ES2369825A1 - Compound with antioxidant activity - Google Patents
Compound with antioxidant activity Download PDFInfo
- Publication number
- ES2369825A1 ES2369825A1 ES201030693A ES201030693A ES2369825A1 ES 2369825 A1 ES2369825 A1 ES 2369825A1 ES 201030693 A ES201030693 A ES 201030693A ES 201030693 A ES201030693 A ES 201030693A ES 2369825 A1 ES2369825 A1 ES 2369825A1
- Authority
- ES
- Spain
- Prior art keywords
- compound according
- compound
- antioxidant
- nmoles
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000003078 antioxidant effect Effects 0.000 title claims abstract description 41
- 150000001875 compounds Chemical class 0.000 title claims description 59
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 claims abstract description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 42
- 239000000203 mixture Substances 0.000 claims description 25
- 239000012453 solvate Substances 0.000 claims description 15
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims description 12
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims description 10
- 235000013305 food Nutrition 0.000 claims description 10
- 229960002748 norepinephrine Drugs 0.000 claims description 10
- 229940002612 prodrug Drugs 0.000 claims description 10
- 239000000651 prodrug Substances 0.000 claims description 10
- 239000002537 cosmetic Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 235000016709 nutrition Nutrition 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 claims description 6
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 claims description 6
- 235000001785 ferulic acid Nutrition 0.000 claims description 6
- 235000013376 functional food Nutrition 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 claims description 5
- 229940114124 ferulic acid Drugs 0.000 claims description 5
- 238000002955 isolation Methods 0.000 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003643 water by type Substances 0.000 claims description 4
- 239000007832 Na2SO4 Substances 0.000 claims description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 claims description 3
- 235000011152 sodium sulphate Nutrition 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 2
- 230000000996 additive effect Effects 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 2
- 230000002441 reversible effect Effects 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- 239000002671 adjuvant Substances 0.000 claims 1
- 241000196324 Embryophyta Species 0.000 description 32
- 235000006708 antioxidants Nutrition 0.000 description 32
- 230000007123 defense Effects 0.000 description 11
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 10
- 239000002207 metabolite Substances 0.000 description 10
- -1 Phenylpropanoid compounds Chemical class 0.000 description 8
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 8
- 244000052769 pathogen Species 0.000 description 8
- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 7
- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 7
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 7
- 235000001368 chlorogenic acid Nutrition 0.000 description 7
- CWVRJTMFETXNAD-JUHZACGLSA-N chlorogenic acid Chemical compound O[C@@H]1[C@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-JUHZACGLSA-N 0.000 description 7
- 229940074393 chlorogenic acid Drugs 0.000 description 7
- FFQSDFBBSXGVKF-KHSQJDLVSA-N chlorogenic acid Natural products O[C@@H]1C[C@](O)(C[C@@H](CC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O FFQSDFBBSXGVKF-KHSQJDLVSA-N 0.000 description 7
- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 7
- 208000015181 infectious disease Diseases 0.000 description 7
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 7
- 240000003768 Solanum lycopersicum Species 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 150000002989 phenols Chemical class 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 5
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 5
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 229930015704 phenylpropanoid Natural products 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical compound C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 4
- 229960005219 gentisic acid Drugs 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 238000002705 metabolomic analysis Methods 0.000 description 4
- 230000001431 metabolomic effect Effects 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 240000008067 Cucumis sativus Species 0.000 description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229930003268 Vitamin C Natural products 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000004665 defense response Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 125000001474 phenylpropanoid group Chemical group 0.000 description 3
- 235000013824 polyphenols Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 235000019154 vitamin C Nutrition 0.000 description 3
- 239000011718 vitamin C Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- NGSWKAQJJWESNS-UHFFFAOYSA-N 4-coumaric acid Chemical compound OC(=O)C=CC1=CC=C(O)C=C1 NGSWKAQJJWESNS-UHFFFAOYSA-N 0.000 description 2
- 241001413795 Actinodaphne acuminata Species 0.000 description 2
- 241000219112 Cucumis Species 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 208000035240 Disease Resistance Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- IHPVFYLOGNNZLA-UHFFFAOYSA-N Phytoalexin Natural products COC1=CC=CC=C1C1OC(C=C2C(OCO2)=C2OC)=C2C(=O)C1 IHPVFYLOGNNZLA-UHFFFAOYSA-N 0.000 description 2
- 241000589615 Pseudomonas syringae Species 0.000 description 2
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 2
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 description 2
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 2
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 235000013734 beta-carotene Nutrition 0.000 description 2
- 239000011648 beta-carotene Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 150000002215 flavonoids Chemical class 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- PUZSUVGRVHEUQO-UHFFFAOYSA-N gentisyl alcohol Chemical compound OCC1=CC(O)=CC=C1O PUZSUVGRVHEUQO-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- ZNJFBWYDHIGLCU-HWKXXFMVSA-N jasmonic acid Chemical compound CC\C=C/C[C@@H]1[C@@H](CC(O)=O)CCC1=O ZNJFBWYDHIGLCU-HWKXXFMVSA-N 0.000 description 2
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000000280 phytoalexin Substances 0.000 description 2
- 150000001857 phytoalexin derivatives Chemical class 0.000 description 2
- 244000000003 plant pathogen Species 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 235000005875 quercetin Nutrition 0.000 description 2
- 229960001285 quercetin Drugs 0.000 description 2
- 235000021283 resveratrol Nutrition 0.000 description 2
- 229940016667 resveratrol Drugs 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 229930000044 secondary metabolite Natural products 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 230000021918 systemic acquired resistance Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 235000014101 wine Nutrition 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 2
- QHGUCRYDKWKLMG-QMMMGPOBSA-N (R)-octopamine Chemical compound NC[C@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-QMMMGPOBSA-N 0.000 description 1
- ZRLYUFOWFPPSTD-QPJJXVBHSA-N (e)-n-[2-(3,4-dihydroxyphenyl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)prop-2-enamide Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)NCCC=2C=C(O)C(O)=CC=2)=C1 ZRLYUFOWFPPSTD-QPJJXVBHSA-N 0.000 description 1
- KZUJJPCTENPKOE-XBXARRHUSA-N (e)-n-[2-(3,4-dihydroxyphenyl)ethyl]-3-(4-hydroxyphenyl)prop-2-enamide Chemical compound C1=CC(O)=CC=C1\C=C\C(=O)NCCC1=CC=C(O)C(O)=C1 KZUJJPCTENPKOE-XBXARRHUSA-N 0.000 description 1
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 241000219194 Arabidopsis Species 0.000 description 1
- 241000219195 Arabidopsis thaliana Species 0.000 description 1
- 241000239290 Araneae Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 102100039339 Atrial natriuretic peptide receptor 1 Human genes 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- JMGZEFIQIZZSBH-UHFFFAOYSA-N Bioquercetin Natural products CC1OC(OCC(O)C2OC(OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5)C(O)C2O)C(O)C(O)C1O JMGZEFIQIZZSBH-UHFFFAOYSA-N 0.000 description 1
- 208000035985 Body Odor Diseases 0.000 description 1
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 description 1
- 235000017647 Brassica oleracea var italica Nutrition 0.000 description 1
- 240000003259 Brassica oleracea var. botrytis Species 0.000 description 1
- 102000012286 Chitinases Human genes 0.000 description 1
- 108010022172 Chitinases Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 235000015510 Cucumis melo subsp melo Nutrition 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 101000961044 Homo sapiens Atrial natriuretic peptide receptor 1 Proteins 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 101000763602 Manilkara zapota Thaumatin-like protein 1 Proteins 0.000 description 1
- 101000763586 Manilkara zapota Thaumatin-like protein 1a Proteins 0.000 description 1
- 241000714212 Melon necrotic spot virus Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001558147 Mortierella sp. Species 0.000 description 1
- 101000966653 Musa acuminata Glucan endo-1,3-beta-glucosidase Proteins 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- QHGUCRYDKWKLMG-MRVPVSSYSA-N Octopamine Natural products NC[C@@H](O)C1=CC=C(O)C=C1 QHGUCRYDKWKLMG-MRVPVSSYSA-N 0.000 description 1
- 241000055229 Penicillium novae-zeelandiae Species 0.000 description 1
- 108700023158 Phenylalanine ammonia-lyases Proteins 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 241001522976 Prunus necrotic ringspot virus Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000208292 Solanaceae Species 0.000 description 1
- 101000611441 Solanum lycopersicum Pathogenesis-related leaf protein 6 Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108010036937 Trans-cinnamate 4-monooxygenase Proteins 0.000 description 1
- 241000726445 Viroids Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- FJJCIZWZNKZHII-UHFFFAOYSA-N [4,6-bis(cyanoamino)-1,3,5-triazin-2-yl]cyanamide Chemical compound N#CNC1=NC(NC#N)=NC(NC#N)=N1 FJJCIZWZNKZHII-UHFFFAOYSA-N 0.000 description 1
- 230000036579 abiotic stress Effects 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000005712 elicitor Substances 0.000 description 1
- IVTMALDHFAHOGL-UHFFFAOYSA-N eriodictyol 7-O-rutinoside Natural products OC1C(O)C(O)C(C)OC1OCC1C(O)C(O)C(O)C(OC=2C=C3C(C(C(O)=C(O3)C=3C=C(O)C(O)=CC=3)=O)=C(O)C=2)O1 IVTMALDHFAHOGL-UHFFFAOYSA-N 0.000 description 1
- 229940093470 ethylene Drugs 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- AHTSCRNWVSEMPI-UHFFFAOYSA-N gold;methane Chemical compound C.[Au] AHTSCRNWVSEMPI-UHFFFAOYSA-N 0.000 description 1
- 201000010235 heart cancer Diseases 0.000 description 1
- 208000024348 heart neoplasm Diseases 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 229930005346 hydroxycinnamic acid Natural products 0.000 description 1
- 235000010359 hydroxycinnamic acids Nutrition 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- ZNJFBWYDHIGLCU-UHFFFAOYSA-N jasmonic acid Natural products CCC=CCC1C(CC(O)=O)CCC1=O ZNJFBWYDHIGLCU-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000000622 liquid--liquid extraction Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000006609 metabolic stress Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 230000007886 mutagenicity Effects 0.000 description 1
- 231100000299 mutagenicity Toxicity 0.000 description 1
- VATOSFCFMOPAHX-XCVCLJGOSA-N n-trans-p-coumaroyloctopamine Chemical compound C=1C=C(O)C=CC=1C(O)CNC(=O)\C=C\C1=CC=C(O)C=C1 VATOSFCFMOPAHX-XCVCLJGOSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229960001576 octopamine Drugs 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000002995 phenylpropanoid derivatives Chemical class 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 230000008640 plant stress response Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 235000020095 red wine Nutrition 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000024428 response to biotic stimulus Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- ALABRVAAKCSLSC-UHFFFAOYSA-N rutin Natural products CC1OC(OCC2OC(O)C(O)C(O)C2O)C(O)C(O)C1OC3=C(Oc4cc(O)cc(O)c4C3=O)c5ccc(O)c(O)c5 ALABRVAAKCSLSC-UHFFFAOYSA-N 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000024053 secondary metabolic process Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- NGSWKAQJJWESNS-ZZXKWVIFSA-N trans-4-coumaric acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C=C1 NGSWKAQJJWESNS-ZZXKWVIFSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C235/34—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Compuesto con actividad antioxidante.Compound with antioxidant activity.
\global\parskip0.900000\baselineskip\ global \ parskip0.900000 \ baselineskip
La presente invención se refiere a un novedoso y potente antioxidante de origen natural, al procedimiento para su obtención y al uso del mismo como antioxidante.The present invention relates to a novel and powerful antioxidant of natural origin, to the procedure for its Obtaining and using it as an antioxidant.
Las plantas, para defenderse de la multitud de potenciales agresiones tanto de naturaleza biótica (patógenos, insectos ...) como abiótica (deficiencia hídrica, salinidad, agentes tóxicos) han desarrollado, a lo largo de la evolución, un sistema de respuesta muy eficaz, formado tanto por defensas inducibles como por barreras constitutivas. Las defensas inducibles constituyen una red multicomponente que integra moléculas de actividad y función biológica diversa, cuya biosíntesis se activa mediante un sistema de señalización, en el que las señales generadas en las interacciones primarias agente agresor-célula convergen hacia un número reducido de señales intermediarias (ácido salicílico, ácido gentísico, etileno, ácido jasmónico, H_{2}O_{2}, NO). Este sistema de defensas inducibles de la planta integra armas defensivas de función muy diversa: generación de especies reactivas de oxígeno, síntesis y deposición de proteínas en la pared celular, necrosis localizada, acumulación de proteínas de defensa (proteínas PR, del inglés Pathogenesis-Related) que incluyen, entre otras, proteínas antimicrobianas del tipo \beta-1,3-glucanasas y quitinasas, así como la producción de metabolitos secundarios defensivos (denominados fitoalexinas) y compuestos fenólicos (Conejero V, Bellés JM, García-Breijo, F, Garro R, Hernández Yago J, Rodrigo I, and Vera P (1990). Signalling in viroid pathogenesis. RSS Fraser (ed). in: Recognition and Response in Plant-Virus Interactions pp 233-261. Springer Verlag, Berlín; Dixon, RA, Harrison, MJ, and Lamb, CJ (1994). Early events in the activation of plant defense response. Ann. Rev. Phytopathol. 32: 479-501; Dixon, RA (2001). Natural Products and plant disease resistence. Nature, 411: 843-847; Kombrink E, and Somssich YE (1995). Defense responses of plants to pathogens. Adv. Bot. Res. 21: 1-34; Ryals JA, Neuenschwander, UH, Willits, MG, Molina A, Steiner H-Y., Hunt MD (1996). Systemic acquired resistance. Plant Cell 8: 1809-1819; Sticher L, Mauch-Mani B, and Métraux JP (1997). Systemic acquired resistance. Annu. Rev. Phytopathol. 35: 235-270; Maleck K, Dietrich RA (1999) Defense on multiple fronts. How do plants cope with diverse enemies? Trends Plant Sci 4: 215-219; Mansfield JW (2000) Antimicrobial compounds and resistance. The role of phytoalexins and phytoanticipins. AJ Slusarenko, RSS Fraser and LC Van Loon (eds). In: Mechanisms of resistance to plant diseases pp 325-370. Kluwer Academic publishers. Netherlands; DangI JL, Jones JDG (2001) Plant pathogens and integrated defence responses to infection. Nature 411: 826-833; Pieterse CM, Van Loon LC. (2004) NPR1: the spider in the web of induced resistance signaling pathways. Curr Opin Plant Biol. 7: 456-64; De Vos M, Van Oosten VR, Van Poecke RM, Van Pelt JA, Pozo MJ, Mueller MJ, Buchala AJ, Métraux JP, Van Loon LC, Dicke M, Pieterse CM. (2005) Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack. Mol Plant Microbe Interact. 18: 923-37; Staal J and Dixelius C (2007). Tracing the ancient origins of plant innate immunity. Trends Plant Sci. 12:334-342).The plants, to defend themselves from the multitude of potential aggressions of both biotic nature (pathogens, insects ...) and abiotic (water deficiency, salinity, toxic agents) have developed, throughout evolution, a very effective response system , formed by both inducible defenses and constitutive barriers. Inducible defenses constitute a multicomponent network that integrates molecules of diverse activity and biological function, whose biosynthesis is activated by a signaling system, in which the signals generated in the primary aggressor-cell interactions converge towards a reduced number of intermediate signals ( salicylic acid, gentisic acid, ethylene, jasmonic acid, H2O2, NO). This system of inducible defenses of the plant integrates defensive weapons of very diverse function: generation of reactive oxygen species, synthesis and deposition of proteins in the cell wall, localized necrosis, accumulation of defense proteins (PR proteins, Pathogenesis-Related English ) which include, among others, antimicrobial proteins of the β-1,3-glucanase and chitinase type, as well as the production of defensive secondary metabolites (called phytoalexins) and phenolic compounds ( Conejero V, Bellés JM, García-Breijo, F, Garro R, Hernández Yago J, Rodrigo I, and Vera P (1990). Signing in viroid pathogenesis. RSS Fraser (ed.) In: Recognition and Response in Plant-Virus Interactions pp 233-261. Springer Verlag, Berlin; Dixon, RA, Harrison, MJ, and Lamb, CJ (1994). Early events in the activation of plant defense response. Ann. Rev. Phytopathol. 32: 479-501; Dixon, RA (2001). Natural Products and plant disease resistence. Nature, 411: 843-8 47; Kombrink E, and Somssich YE (1995). Defense responses of plants to pathogens. Adv. Bot. Res. 21: 1-34; Ryals JA, Neuenschwander, UH, Willits, MG, Molina A, Steiner HY., Hunt MD (1996). Systemic acquired resistance. Plant Cell 8: 1809-1819; Sticher L, Mauch-Mani B, and Métraux JP (1997). Systemic acquired resistance. Annu Rev. Phytopathol. 35: 235-270; Maleck K, Dietrich RA (1999) Defense on multiple fronts. How do plants cope with diverse enemies? Trends Plant Sci 4: 215-219; Mansfield JW (2000) Antimicrobial compounds and resistance. The role of phytoalexins and phytoanticipins. AJ Slusarenko, RSS Fraser and LC Van Loon (eds). In: Mechanisms of resistance to plant diseases pp 325-370. Kluwer Academic publishers. Netherlands; DangI JL, Jones JDG (2001) Plant pathogens and integrated defense responses to infection. Nature 411: 826-833; Pieterse CM, Van Loon LC. (2004) NPR1: the spider in the web of induced resistance signaling pathways. Curr Opin Plant Biol. 7: 456-64; De Vos M, Van Oosten VR, Van Poecke RM, Van Pelt JA, Pozo MJ, Mueller MJ, Buchala AJ, Métraux JP, Van Loon LC, Dicke M, Pieterse CM. (2005) Signal signature and transcriptome changes of Arabidopsis during pathogen and insect attack. Mol Plant Microbe Interact. 18: 923-37; Staal J and Dixelius C (2007). Tracing the ancient origins of plant innate immunity. Trends Plant Sci. 12: 334-342 ).
Existen numerosas referencias bibliográficas en las que se discute sobre la implicación de una serie de metabolitos secundarios como componentes de defensa inducibles y constitutivos de la planta (Metraux JP and Raskin I (1993). Role of phenolics in plant disease resistance. Biotechnology in Plant Disease Control 191-209; Dixon, RA (2001). Natural Products and plant disease resistence. Nature, 411: 843-847; Singer AC, Crowley D, Thompson IP (2003). Secondary plant metabolites in phytoremediation and biotransformation. Trends in Biotechnology 21: 123-130; Kliedenstein, 2004). Su papel defensivo frente a patógenos está bien establecido; en cambio, se conoce menos su posible función en la señalización de la respuesta defensiva inducible (Zhao J, Davis LC, Verpoorte R (2005). Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnology Advances, 23: 283-333; Lewis K, and Ausubel FM (2006). Prospects for plant-derived antibacterials. Nature Biotechnology, 24: 1504-1507).There are numerous bibliographical references that discuss the implication of a series of secondary metabolites as inducible and constitutive defense components of the plant ( Metraux JP and Raskin I (1993). Role of phenolics in plant disease resistance. Biotechnology in Plant Disease Control 191-209; Dixon, RA (2001). Natural Products and plant disease resistence. Nature, 411: 843-847; Singer AC, Crowley D, Thompson IP (2003). Secondary plant metabolites in phytoremediation and biotransformation. Trends in Biotechnology 21: 123-130; Kliedenstein, 2004 ). Its defensive role against pathogens is well established; on the other hand, its possible role in signaling the inducible defensive response is less known ( Zhao J, Davis LC, Verpoorte R (2005). Elicitor signal transduction leading to production of plant secondary metabolites. Biotechnology Advances, 23: 283-333; Lewis K, and Ausubel FM (2006). Prospects for plant-derived antibacterials. Nature Biotechnology, 24: 1504-1507 ).
A lo largo de los últimos años, se han realizado estudios dirigidos a elucidar la implicación de compuestos del metabolismo secundario en la interacción de plantas de tomate con distintos patógenos. Esto ha permitido detectar cambios concretos de los niveles de un número determinado de metabolitos a lo largo de las infecciones, entre los que cabe destacar la identificación del ácido gentísico (GA) (2,5-dihidroxibenzoico), derivado biosintético del ácido salicílico (SA) (Bellés JM, Garro R, Fayos J, Navarro P, Primo J, Conejero V (1999) Gentisisc acid as a pathogen-inducible signal additional to salicylic acid for activation of plant defenses in tomato. Mol. Plant-Microbe Interact. 12:227-235; Bellés J.M, Garro R, Pallás V, Fayos J, Rodrigo I, Conejero, V. (2006) Accumulation of gentisic acid as associated with systemic infections but not with the hypersensitive response in plant-pathogen interactions. Planta 223:500-511; Fayos J, Bellés JM, López-Gresa MP, Primo J, Conejero V (2006). Induction of gentisic acid 5-O-\beta-D-xylopyranoside in tomato and cucumber plants infected by different pathogens. Phytochemistry, 67: 142-148). Asimismo, se han aislado a partir de plantas de tomate varias nuevas amidas derivadas del ácido hidroxicinámico, como respuesta a la infección por la bacteria Pseudomonas syringae (Zacarés, L, López-Gresa MP, Fayos J, Primo J, Bellés JM, Conejero V (2008). Induction of p-coumaroyldopamine and feruloyldopamine, two novel metabolites en tomato by the bacterial pathogen Pseudomonas syringae. Mol. Plant-Microbe Interact. 20: 1439-1448). Recientemente, también en nuestro laboratorio, se ha estudiado la inducción de varios compuestos fenólicos en plantas de melón y pepino tras la infección por los virus necróticos MNSV y PNRSV, respectivamente (Bellés JM, López-Gresa MP, Fayos J, Pallás V, Rodrigo I, Conejero V. (2008) Induction of cinnamate 4-hydroxylase and phenylpropanoids in virus-infected cucumber and melón plants. Plant Science 174:524-533).Over the past few years, studies have been conducted to elucidate the involvement of secondary metabolism compounds in the interaction of tomato plants with different pathogens. This has allowed the detection of specific changes in the levels of a certain number of metabolites throughout the infections, among which the identification of gentysic acid (GA) (2,5-dihydroxybenzoic acid), biosynthetic derivative of salicylic acid (SA) ) ( Bellés JM, Garro R, Fayos J, Navarro P, Primo J, Conejero V (1999) Gentisisc acid as a pathogen-inducible signal additional to salicylic acid for activation of plant defenses in tomato. Mol. Plant-Microbe Interact. 12 : 227-235; Bellés JM, Garro R, Pallás V, Fayos J, Rodrigo I, Conejero, V. (2006) Accumulation of gentisic acid as associated with systemic infections but not with the hypersensitive response in plant-pathogen interactions. : 500-511; Fayos J, Bellés JM, López-Gresa MP, Primo J, Conejero V (2006). Induction of gentisic acid 5-O-? -D-xylopyranoside in tomato and cucumber plants infected by different pathogens. Phytochemistry , 67: 142-148 ). Likewise, several new amides derived from hydroxycinnamic acid have been isolated from tomato plants, in response to infection by Pseudomonas syringae bacteria ( Zacarés, L, López-Gresa MP, Fayos J, Primo J, Bellés JM, Conejero V (2008) Induction of p-coumaroyldopamine and feruloyldopamine, two novel metabolites in tomato by the bacterial pathogen Pseudomonas syringae, Mol. Plant-Microbe Interact, 20: 1439-1448 ). Recently, also in our laboratory, the induction of several phenolic compounds in melon and cucumber plants after infection with the MNSV and PNRSV necrotic viruses, respectively ( Bellés JM, López-Gresa MP, Fayos J, Pallás V, Rodrigo) has been studied I, Conejero V. (2008) Induction of cinnamate 4-hydroxylase and phenylpropanoids in virus-infected cucumber and melon plants. Plant Science 174: 524-533 ).
Mediante las actuales técnicas aplicadas en metabolómica se puede investigar de un modo global los metabolitos implicados y sus posibles interacciones en la infección (Sumner LW, Mendes P, Dixon RA. (2003) Plant metabolomics: large-scale phytochemistry in the functional genomics era. Phytochemistry. 62: 817-36; Verpoorte, R, Choi, YH, Mustafa, NR, Kim, HK. (2008) Metabolomics: back to basics. Phytochemistry Reviews 7: 525-537). Los cambios en los niveles de estos compuestos marcadores del estrés metabólico podrían estar correlacionados con cambios en el transcriptoma y proteoma que podrían ser confirmados mediante el análisis de mutantes (Shulaev V, Cortes D, Miller G, Mittler R. (2008) Metabolomics for plant stress response. Physiologia Plantarum 132: 199-208). Es por esto por lo que importantes laboratorios están activamente implicados en la búsqueda y caracterización de metabolitos producidos por las plantas y en el estudio de su papel en la resistencia de las mismas frente a diferentes situaciones de estrés (Von Roepenack-Lahaye E, Newman MA, Schornack S, Hammond-Kosack KE, Lahaye T, Jones JD, Daniels MJ, Dow JM. (2003) p-Coumaroylnoradrenaline, a novel plant metabolite implicated in tomato defense against pathogens. J Biol Chem. 278: 43373-83; Hahlbrock K, Bednarek P, Ciolkowski I, Hamberger B, Heise A, Liedgens H, Logemann E, Nurnberger T, Schmelzer E, Somssich IE, Tan J. (2003) Non-self recognition, transcriptional reprogramming, and secondary metabolite accumulation during plant/pathogen interactions. Proc Natl Acad Sci U S A. 100: 14569-76; Shadle GL, Wesley SV, Korth KL, Chen F, Lamb C, Dixon RA. (2003) Phenylpropanoid compounds and disease resistance in transgenic tobacco with altered expression of L-phenylalanine ammonia-lyase. Phytochemistry. 64: 153-61; Tan J, Bednarek P, Liu J, Schneider B, Svatos A, Hahlbrock K. (2004) Universally occurring phenylpropanoid and species-specific indolic metabolites in infected and uninfected Arabidopsis thaliana roots and leaves. Phytochemistry 65: 691-9).Through the current techniques applied in metabolomics, the metabolites involved and their possible interactions in the infection can be investigated in a global way ( Sumner LW, Mendes P, Dixon RA. (2003) Plant metabolomics: large-scale phytochemistry in the functional genomics era. Phytochemistry 62: 817-36; Verpoorte, R, Choi, YH, Mustafa, NR, Kim, HK. (2008) Metabolomics: back to basics. Phytochemistry Reviews 7: 525-537 ). Changes in the levels of these metabolic stress marker compounds could be correlated with changes in the transcriptome and proteome that could be confirmed by mutant analysis ( Shulaev V, Cortes D, Miller G, Mittler R. (2008) Metabolomics for plant stress response Physiology Plantarum 132: 199-208 ). This is why important laboratories are actively involved in the search and characterization of metabolites produced by plants and in the study of their role in their resistance to different stress situations ( Von Roepenack-Lahaye E, Newman MA , Schornack S, Hammond-Kosack KE, Lahaye T, Jones JD, Daniels MJ, Dow JM. (2003) p-Coumaroylnoradrenaline, a novel plant metabolite implicated in tomato defense against pathogens. J Biol Chem. 278: 43373-83; Hahlbrock K, Bednarek P, Ciolkowski I, Hamberger B, Heise A, Liedgens H, Logemann E, Nurnberger T, Schmelzer E, Somssich IE, Tan J. (2003) Non-self recognition, transcriptional reprogramming, and secondary metabolite accumulation during plant / pathogen interactions Proc Natl Acad Sci US A. 100: 14569-76; Shadle GL, Wesley SV, Korth KL, Chen F, Lamb C, Dixon RA. (2003) Phenylpropanoid compounds and disease resistance in transgenic tobacco with altered expression of L -phenylalanine ammonia-lyase. Phytochemistry 64: 153-61; Tan J, Bednarek P, Liu J, Schneider B, Svatos A, Hahlbrock K. (2004) Universally occurring phenylpropanoid and species-specific indolic metabolites in infected and uninfected Arabidopsis thaliana roots and leaves. Phytochemistry 65: 691-9 ).
El estudio de estos metabolitos contribuye al conocimiento del sistema defensivo de las plantas frente a patógenos y otros agentes estresantes, tanto en sus aspectos de señalización como en los que se refieren a los componentes de la respuesta final de la planta.The study of these metabolites contributes to knowledge of the defense system of plants against pathogens and other stressful agents, both in their aspects of signaling as in those referring to the components of the final answer of the plant.
Por otra parte, estas moléculas inducidas tras una infección poseen frecuentemente algún tipo de actividad biológica (antibacteriana, antifúngica, antioxidante o insecticida) generando de este modo compuestos de interés para la industria química, agroquímica, farmacéutica, nutricional o cosmética. Así, los compuestos fenólicos, que son producidos por la plantas en respuesta a estreses bióticos o abióticos, poseen múltiples efectos, tales como su actividad antioxidante (Niggeweg R, Michael AJ, Martin C (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid. Nat. Biotechnol. 22: 746-754). De hecho, las bases moleculares de su acción protectora en la respuesta a estrés se basan precisamente en sus propiedades antioxidantes y de secuestro (scavenging) de radicales libres (Korkina LG (2007). Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health. Cell Mol Biol. 53 (1):15-25). Tal es el caso del ácido clorogénico (CGA), un flavonoide muy abundante en Solanáceas que se induce tras una infección bacteriana y que resulta ser un potente antioxidante. Además de los compuestos fenólicos, se ha descrito en plantas la presencia de otras sustancias de elevado poder antioxidante como el ácido ascórbico (vitamina C), el tocoferol (vitamina E) o el \beta-caroteno (provitamina A).On the other hand, these molecules induced after infection frequently have some type of biological activity (antibacterial, antifungal, antioxidant or insecticide) thus generating compounds of interest to the chemical, agrochemical, pharmaceutical, nutritional or cosmetic industry. Thus, phenolic compounds, which are produced by plants in response to biotic or abiotic stresses, have multiple effects, such as their antioxidant activity ( Niggeweg R, Michael AJ, Martin C (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid, Nat. Biotechnol. 22: 746-754 ). In fact, the molecular basis of its protective action in the stress response is based precisely on its antioxidant and scavenging properties of free radicals ( Korkina LG (2007). Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health Cell Mol Biol. 53 (1): 15-25 ). Such is the case of chlorogenic acid (CGA), a flavonoid very abundant in Solanaceae that is induced after a bacterial infection and that turns out to be a potent antioxidant. In addition to phenolic compounds, the presence of other substances of high antioxidant power such as ascorbic acid (vitamin C), tocopherol (vitamin E) or β-carotene (provitamin A) has been described in plants.
En los últimos años se ha despertado un gran interés por los antioxidantes naturales. La industria alimentaria los emplea porque retrasan la oxidación de lípidos y, por lo tanto, mejoran la calidad nutricional de los alimentos. Asimismo, los antioxidantes poseen propiedades beneficiosas para la salud, entre las que cabe destacar la prevención de las enfermedades coronarias y el cáncer. Por último, se emplean en la industria cosmética como ingredientes naturales activos. (Kähkönen MP, Hopia Al, Vuorela HJ, Rauha JP, Pihlaja K, Kujala TS, Heinonen M (1999). Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem. 47 (10):3954-62; Korkina LG (2007). Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health. Cell Mol Biol. 53 (1):15-25). Asimismo, la obtención de nuevos metabolitos de origen vegetal con propiedades antioxidantes resulta también de máximo interés, en la industria química, y, especialmente, en la industria del caucho, de los polímeros o de la energía.In recent years a great interest in natural antioxidants has been aroused. The food industry uses them because they delay the oxidation of lipids and, therefore, improve the nutritional quality of food. Likewise, antioxidants have beneficial properties for health, including the prevention of coronary heart disease and cancer. Finally, they are used in the cosmetic industry as active natural ingredients. ( Kähkönen MP, Hopia Al, Vuorela HJ, Rauha JP, Pihlaja K, Kujala TS, Heinonen M (1999). Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem. 47 (10): 3954-62; Korkina LG (2007) Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health. Cell Mol Biol. 53 (1): 15-25 ). Likewise, obtaining new metabolites of plant origin with antioxidant properties is also of maximum interest, in the chemical industry, and especially in the rubber, polymer or energy industry.
La presente invención se refiere a un novedoso y potente antioxidante de origen natural que mejora de manera extraordinaria los valores obtenidos por otros compuestos antioxidantes conocidos. Además, se describe el procedimiento para su obtención y el uso del mismo como antioxidante en el sector químico, farmacéutico, cosmético, nutricional, entre otros.The present invention relates to a novel and powerful antioxidant of natural origin that improves so extraordinary values obtained by other compounds known antioxidants In addition, the procedure for describing Obtaining and using it as an antioxidant in the sector Chemical, pharmaceutical, cosmetic, nutritional, among others.
Por lo tanto un primer aspecto fundamental de la presente invención se refiere al compuesto de fórmula (I), feruloilnoradrenalina, que tiene la siguiente estructura:Therefore a first fundamental aspect of the The present invention relates to the compound of formula (I), Feruloylnoradrenaline, which has the following structure:
o cualquiera de sus isómeros, sales, o solvatos.or any of its isomers, go out, or Solvates
\global\parskip1.000000\baselineskip\ global \ parskip1.000000 \ baselineskip
El compuesto de la presente invención puede incluir isómeros geométricos (denominados Z/E o cis/trans) y ópticos (denominados R/S), dependiendo de la presencia de centros quirales. Cualquiera de los isómeros posibles y las mezclas de los mismos caen dentro del alcance de la presente invención.The compound of the present invention may include geometric (called Z / E or cis / trans ) and optical isomers (called R / S ), depending on the presence of chiral centers. Any of the possible isomers and mixtures thereof fall within the scope of the present invention.
Según otra realización preferida, el compuesto de la presente invención es la trans-feruloilnoradrenalina, es decir, el (R,E)-N-(2-(3,4-dihidroxifenil)-2-hidrixietil)-3-(4-hidroxi-3-metoxifenil)acrilamida, de estructura:According to another preferred embodiment, the compound of the present invention is trans -feruloylnoradrenaline, that is, ( R, E ) - N - (2- (3,4-dihydroxyphenyl) -2-hydroxyethyl) -3- (4- hydroxy-3-methoxyphenyl) acrylamide, of structure:
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
El compuesto de la invención puede estar en forma cristalina como compuesto libre o como solvato. En este sentido, el término "solvato", tal como aquí se utiliza, incluye tanto solvatos farmacéuticamente aceptables, es decir, solvatos del compuesto que pueden ser utilizados en la elaboración de un medicamento, como solvatos farmacéuticamente no aceptables, los cuales pueden ser útiles en la preparación de solvatos o sales farmacéuticamente aceptables. La naturaleza del solvato farmacéuticamente aceptable no es crítica siempre y cuando sea farmacéuticamente aceptable. En una realización particular, el solvato es un hidrato. Los solvatos pueden obtenerse por métodos convencionales de solvatación conocidos por los expertos en la materia.The compound of the invention may be in crystalline form as free compound or as solvate. In this meaning, the term "solvate", as used here, includes both pharmaceutically acceptable solvates, that is, compound solvates that can be used in manufacturing of a medication, such as pharmaceutically acceptable solvates, which can be useful in the preparation of solvates or salts pharmaceutically acceptable. The nature of the solvato pharmaceutically acceptable is not critical as long as it is pharmaceutically acceptable. In a particular embodiment, the Solvate is a hydrate. Solvates can be obtained by methods conventional solvation known by experts in the matter.
Asimismo, dentro del alcance de esta invención se encuentra el profármaco del compuesto descrito anteriormente. El término "prodroga" o "profármaco" tal como aquí se utiliza incluye el compuesto derivado del compuesto descrito anteriormente -por ejemplo y no limitativamente: ésteres (incluyendo ésteres de ácidos carboxílicos, ésteres de aminoácidos, ésteres de fosfato, ésteres de sulfonato de sales metálicas, etc.), carbamatos, amidas, etc.- que al ser administrado a un individuo puede ser transformado directa o indirectamente en dicho compuesto en el mencionado individuo. Ventajosamente, dicho derivado es un compuesto que aumentaría la biodisponibilidad del compuesto cuando se administra a un individuo o que potenciaría la liberación del compuesto en un compartimento biológico. La naturaleza de dicho derivado no es crítica siempre y cuando pueda ser administrado a un individuo y proporcione el compuesto en un compartimento biológico. La preparación de dicho profármaco puede llevarse a cabo mediante métodos convencionales conocidos por los expertos en la materia.Also, within the scope of this invention the prodrug of the compound described above is found. He term "prodrug" or "prodrug" as used herein includes the compound derived from the compound described above -for example and not limitation: esters (including esters of carboxylic acids, amino acid esters, phosphate esters, sulphonate esters of metal salts, etc.), carbamates, amides, etc.- that when administered to an individual can be transformed directly or indirectly in said compound in the mentioned individual. Advantageously, said derivative is a compound that would increase the bioavailability of the compound when administered to an individual or that would enhance the release of the compound in a biological compartment The nature of said derivative is not criticism as long as it can be administered to an individual and provide the compound in a biological compartment. The preparation of said prodrug can be carried out by Conventional methods known to those skilled in the art.
Para su aplicación en terapia, el compuesto, sus sales, profármacos o solvatos, se encontrarán, preferentemente, en una forma farmacéuticamente aceptable o sustancialmente pura, es decir, que tiene un nivel de pureza farmacéuticamente aceptable excluyendo los aditivos farmacéuticos normales tales como diluyentes y portadores, y no incluyendo material considerado tóxico a niveles de dosificación normales. Los niveles de pureza para el principio activo son preferiblemente superiores al 50%, más preferiblemente superiores al 70%, y todavía más preferiblemente superiores al 90%. En una realización preferida, son superiores al 95% del compuesto anteriormente descrito, o de sus sales, solvatos o profármacos.For its application in therapy, the compound, its salts, prodrugs or solvates, will preferably be found in a pharmaceutically acceptable or substantially pure form, is say, it has a pharmaceutically acceptable level of purity excluding normal pharmaceutical additives such as diluents and carriers, and not including material considered toxic at levels of normal dosage. Purity levels for the beginning active are preferably greater than 50%, more preferably greater than 70%, and still more preferably greater than 90%. In a preferred embodiment, they are greater than 95% of the compound previously described, or of its salts, solvates or prodrugs.
En otro aspecto, la presente invención también se refiere a las composiciones farmacéuticas que comprenden al menos un compuesto de la invención, o un tautómero, una sal farmacéuticamente aceptable, un derivado o un profármaco del mismo, junto con un transportador o carrier farmacéuticamente aceptable, un excipiente o un vehículo, para la administración a un paciente.In another aspect, the present invention also refers to pharmaceutical compositions comprising at least a compound of the invention, or a tautomer, a salt pharmaceutically acceptable, a derivative or a prodrug thereof, together with a pharmaceutically acceptable carrier or carrier, a excipient or a vehicle, for administration to a patient.
En una realización preferida, la composición farmacéutica comprende además otro principio activo.In a preferred embodiment, the composition Pharmaceutical also includes another active ingredient.
Los adyuvantes y vehículos farmacéuticamente aceptables que pueden ser utilizados en dichas composiciones serán aquellos conocidos por los técnicos en la materia y utilizados habitualmente en la elaboración de composiciones terapéuticas.Pharmaceutical adjuvants and vehicles acceptable that can be used in said compositions will be those known to those skilled in the art and used usually in the elaboration of therapeutic compositions.
El compuesto descrito en la presente invención, sus sales, profármacos y/o solvatos así como las composiciones farmacéuticas, cosméticas y nutricionales que los contienen pueden ser utilizados junto con otros fármacos, o principios activos, adicionales para proporcionar una terapia de combinación. Dichos fármacos adicionales pueden formar parte de la misma composición farmacéutica o, alternativamente, pueden ser proporcionados en forma de una composición separada para su administración simultánea o no a la de la composición farmacéutica que comprende el compuesto anteriormente descrito, o una sal, profármaco o solvato del mismo.The compound described in the present invention, its salts, prodrugs and / or solvates as well as the compositions Pharmaceutical, cosmetic and nutritional products that contain them can be used together with other drugs, or active ingredients, additional to provide a combination therapy. Sayings Additional drugs may be part of the same composition pharmaceutical or, alternatively, can be provided in of a separate composition for simultaneous administration or not to that of the pharmaceutical composition comprising the compound previously described, or a salt, prodrug or solvate of the same.
En una realización preferida de la presente invención, las composiciones farmacéuticas son adecuadas para la administración oral, en forma sólida o líquida. Las posibles formas para la administración oral son tabletas, cápsulas, siropes o soluciones y pueden contener excipientes convencionales conocidos en el ámbito farmacéutico, como agentes agregantes (p.e. sirope, acacia, gelatina, sorbitol, tragacanto o polivinil pirrolidona), rellenos (p.e. lactosa, azúcar, almidón de maíz, fosfato de calcio, sorbitol o glicina), disgregantes (p.e. almidón, polivinil pirrolidona o celulosa microcristalina) o un surfactante farmacéuticamente aceptable como el lauril sulfato de sodio.In a preferred embodiment of the present invention, the pharmaceutical compositions are suitable for the oral administration, in solid or liquid form. The possible ways for oral administration are tablets, capsules, syrups or solutions and may contain conventional excipients known in the pharmaceutical field, as aggregating agents (e.g. syrup, acacia, gelatin, sorbitol, tragacanth or polyvinyl pyrrolidone), fillers (e.g. lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine), disintegrants (e.g. starch, polyvinyl pyrrolidone or microcrystalline cellulose) or a surfactant Pharmaceutically acceptable as sodium lauryl sulfate.
Las composiciones para administración oral pueden ser preparadas por métodos los convencionales de Farmacia Galénica, como mezcla y dispersión. Las tabletas se pueden recubrir siguiendo métodos conocidos en la industria farmacéutica.Compositions for oral administration can be prepared by conventional methods of Pharmacy Galenic, as a mixture and dispersion. The tablets can be coated following methods known in the pharmaceutical industry.
Las composiciones farmacéuticas se pueden adaptar para la administración parenteral, como soluciones estériles, suspensiones, o liofilizados de los productos de la invención, empleando la dosis adecuada. Se pueden emplear excipientes adecuados, como agentes tamponadores del pH o surfactantes.Pharmaceutical compositions can be adapt for parenteral administration, as solutions sterile, suspensions, or lyophilized products of the invention, using the appropriate dose. Can be used suitable excipients, such as pH buffering agents or surfactants
Las formulaciones anteriormente mencionadas pueden ser preparadas usando métodos convencionales, como los descritos en las Farmacopeas de diferentes países y en otros textos de referencia.The aforementioned formulations they can be prepared using conventional methods, such as described in the Pharmacopoeias of different countries and in other texts reference.
La administración de los compuestos o composiciones de la presente invención puede ser realizada mediante cualquier método adecuado, como la infusión intravenosa y las vías oral, intraperitoneal o intravenosa. La administración oral es la preferida por la conveniencia de los pacientes y por el carácter crónico de las enfermedades a tratar.The administration of the compounds or Compositions of the present invention can be made by any suitable method, such as intravenous infusion and routes oral, intraperitoneal or intravenous. Oral administration is the preferred for patient convenience and for character Chronic diseases to be treated.
La cantidad administrada de un compuesto de la presente invención dependerá de la relativa eficacia del compuesto elegido, la severidad de la enfermedad a tratar y el peso del paciente. Sin embargo, los compuestos de esta invención serán administrados una o más veces al día, por ejemplo 1, 2, 3 ó 4 veces diarias, con una dosis total entre 0.1 y 1000 mg/Kg/día. Es importante tener en cuenta que puede ser necesario introducir variaciones en la dosis, dependiendo de la edad y de la condición del paciente, así como modificaciones en la vía de administración.The administered amount of a compound of the The present invention will depend on the relative efficacy of the compound. chosen, the severity of the disease to be treated and the weight of the patient. However, the compounds of this invention will be administered one or more times a day, for example 1, 2, 3 or 4 times daily, with a total dose between 0.1 and 1000 mg / kg / day. Is important to keep in mind that it may be necessary to introduce dose variations, depending on age and condition of the patient, as well as modifications in the route of administration.
Los compuestos y composiciones de la presente invención pueden ser empleados junto con otros medicamentos en terapias combinadas. Los otros fármacos pueden formar parte de la misma composición o de otra composición diferente, para su administración al mismo tiempo o en tiempos diferentes.The compounds and compositions herein invention can be used together with other medications in Combined therapies The other drugs may be part of the same or different composition, for your administration at the same time or at different times.
Según otra realización preferida, se refiere a una composición cosmética que comprende al menos el compuesto de fórmula (I) o su isómero trans R.According to another preferred embodiment, it refers to a cosmetic composition comprising at least the compound of formula (I) or its trans isomer R.
Según otra realización preferida, se refiere a una composición nutricional que comprende al menos el compuesto de fórmula (I) o su isómero trans R.According to another preferred embodiment, it refers to a nutritional composition comprising at least the compound of formula (I) or its trans isomer R.
Un segundo aspecto esencial de la presente invención se refiere a la síntesis química de la feruloilnoradrenalina, más preferiblemente de la trans-feruloilnoradrenalina.A second essential aspect of the present invention relates to the chemical synthesis of feruloylnoradrenaline, more preferably trans -feruloylnoradrenaline.
La síntesis química de este compuesto comprende hacer reaccionar mezclando el ácido ferúlico (ácido 4-hidroxi-3-metoxicinámico) con la noradrenalina (2-[3,4-dihidroxifenil]-2-hidroxietilamina) con dimetilformamida, en presencia del catalizador N, N'-diciclohexilcarbodiimida (DCC), siguiendo el método descrito en Tanaka H, Takeshi N, Kazuhiko I, Kazuo I (1989) A phenolic amide from Actinodaphne longifolia. Phytochemistry 289: 2516-2517.The chemical synthesis of this compound comprises reacting by mixing the ferulic acid (4-hydroxy-3-methoxycinnamic acid) with norepinephrine (2- [3,4-dihydroxyphenyl] -2-hydroxyethylamine) with dimethylformamide, in the presence of catalyst N, N'-dicyclohexylcarbodiimide (DCC), following the method described in Tanaka H, Takeshi N, Kazuhiko I, Kazuo I (1989) A phenolic amide from Actinodaphne longifolia. Phytochemistry 289: 2516-2517 .
Según una realización preferida, tras hacer reaccionar ambos compuestos con el catalizador, se llevan a cabo las siguientes etapas:According to a preferred embodiment, after doing reacting both compounds with the catalyst, the following stages:
- --
- Dejar reaccionar toda la noche a temperatura ambiente.Leave react overnight at room temperature.
- --
- Eliminar los disolventes.Remove solvents.
- --
- Realizar una extracción líquido-líquido con agua y acetato de etilo.Perform an extraction liquid-liquid with water and acetate ethyl.
- --
- Secar la fase orgánica con Na_{2}SO_{4} anhidro.Dry off the organic phase with anhydrous Na2SO4.
- --
- Filtrar y evaporar hasta la obtención de un aceite viscoso.Filter and evaporate until obtaining a viscous oil.
- --
- Purificar el aceite hasta el aislamiento de la feruloilnoradrenalina, mediante una columna de silicagel flash (Merck, 0,040-0,063 mm), utilizando como fase móvil una mezcla de hexano/acetato de etilo (1:1).Purify the oil until isolation of the feruloylnoradrenaline, using a flash silica gel column (Merck, 0.040-0.063 mm), using as mobile phase a hexane / ethyl acetate mixture (1: 1).
- --
- El aislamiento final del compuesto se realiza mediante HPLC (Waters 600E) acoplado a un detector PDA en una columna preparativa de fase reversa C18 SymmetryPrep 7 \mum (19 x 150 mm, Waters) a temperatura ambiente y en condiciones isocráticas usando una mezcla de MeOH y 1% ácido acético (25:75) a un flujo de 10 ml/min. En estas condiciones el compuesto tiene un tiempo de retención de 28.4 min.He Final isolation of the compound is done by HPLC (Waters 600E) coupled to a PDA detector in a phase preparative column reverse C18 SymmetryPrep 7 \ mum (19 x 150 mm, Waters) a room temperature and in isocratic conditions using a mixture of MeOH and 1% acetic acid (25:75) at a flow of 10 ml / min. In these conditions the compound has a retention time of 28.4 min.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
Según otra realización preferida se añaden desde 0,1 a 1 nmol del ácido ferúlico, preferiblemente desde 0,3 a 0,7 nmoles y más preferiblemente 0,5 nmoles.According to another preferred embodiment they are added from 0.1 to 1 nmol of the ferulic acid, preferably from 0.3 to 0.7 nmoles and more preferably 0.5 nmoles.
Según otra realización preferida se añaden desde 0,3 a 1,2 nmoles de la noradrenalina, preferiblemente desde 0,5 a 0,8 nmoles y más preferiblemente 0,65 nmoles.According to another preferred embodiment they are added from 0.3 to 1.2 nmoles of norepinephrine, preferably from 0.5 to 0.8 nmoles and more preferably 0.65 nmoles.
Según otra realización preferida, el ácido ferúlico y la noradrenalina se mezclan en una cantidad de dimetilformamida (DMF) desde 10 a 3 ml, preferiblemente desde 15 a 25 ml y más preferiblemente en 20 ml.According to another preferred embodiment, the acid ferulic and norepinephrine are mixed in an amount of dimethylformamide (DMF) from 10 to 3 ml, preferably from 15 to 25 ml and more preferably in 20 ml.
Según otra realización preferida, se añade una cantidad del catalizador (DCC) desde 0,3 a 1,2 nmol en desde 2 a 7 ml de DMF, preferiblemente desde 0,6 a 0,9 nmol en desde 3,5 a 5,7 ml de DMF, preferiblemente 0,8 nmol en 5 ml de DMF.According to another preferred embodiment, a Catalyst amount (DCC) from 0.3 to 1.2 nmol in from 2 to 7 ml of DMF, preferably from 0.6 to 0.9 nmol in from 3.5 to 5.7 ml of DMF, preferably 0.8 nmol in 5 ml of DMF.
Un cuarto aspecto esencial de la presente invención se refiere al uso de la feruloilnoradrenalina, más preferiblemente la trans-feruloilnoradrenalina, como antioxidante.A fourth essential aspect of the present invention relates to the use of feruloylnoradrenaline, more preferably trans-feruloylnoradrenaline, as antioxidant
Según otra realización preferida, la feruloilnoradrenalina, y más preferiblemente la trans-feruloilnoradrenalina, se usa en la fabricación de un medicamento.According to another preferred embodiment, feruloylnoradrenaline, and more preferably trans -feruloylnoradrenaline, is used in the manufacture of a medicament.
Según otra realización preferida, la feruloilnoradrenalina, y más preferiblemente la trans-feruloilnoradrenalina, se usa para la fabricación de un cosmético.According to another preferred embodiment, feruloylnoradrenaline, and more preferably trans -feruloylnoradrenaline, is used for the manufacture of a cosmetic.
Según otra realización preferida, la feruloilnoradrenalina, y más preferiblemente la trans-feruloilnoradrenalina, se usa como aditivo en alimentos funcionales.According to another preferred embodiment, feruloylnoradrenaline, and more preferably trans -feruloylnoradrenaline, is used as an additive in functional foods.
Según otra realización preferida, la feruloilnoradrenalina, y más preferiblemente la trans-feruloilnoradrenalina, se usa para la fabricación de un alimento funcional.According to another preferred embodiment, feruloylnoradrenaline, and more preferably trans -feruloylnoradrenaline, is used for the manufacture of a functional food.
Según otra realización preferida, la feruloilnoradrenalina, y más preferiblemente la trans-feruloilnoradrenalina, se usa como bloqueador de radicales libres.According to another preferred embodiment, feruloylnoradrenaline, and more preferably trans -feruloylnoradrenaline, is used as a free radical blocker.
Según otra realización preferida, la feruloilnoradrenalina, y más preferiblemente la trans-feruloilnoradrenalina, se usa como antioxidante en la industria química del caucho, de los polímeros y de la energía.According to another preferred embodiment, feruloylnoradrenaline, and more preferably trans -feruloylnoradrenaline, is used as an antioxidant in the chemical industry of rubber, polymers and energy.
En el sentido utilizado en esta descripción, la expresión "cantidad terapéuticamente efectiva" se refiere a la cantidad del agente o compuesto capaz de desarrollar la acción terapéutica determinada por sus propiedades farmacológicas, calculada para producir el efecto deseado y, en general, vendrá determinada, entre otras causas, por las características propias de los compuestos, incluyendo la edad, estado del paciente, la severidad de la alteración o trastorno, y de la ruta y frecuencia de administración.In the sense used in this description, the expression "therapeutically effective amount" refers to the amount of agent or compound capable of carrying out the action therapeutic determined by its pharmacological properties, calculated to produce the desired effect and, in general, will come determined, among other causes, by the characteristics of the compounds, including the age, condition of the patient, the severity of the alteration or disorder, and of the route and frequency of administration.
En la presente invención se entiende como "alimento funcional", un alimento que posee un efecto beneficioso sobre la salud. Del mismo modo, el término alimento funcional puede aplicarse a extractos o compuestos químicos obtenidos de alimentos comunes. Ejemplos de alimentos a los que se les atribuyen propiedades funcionales son el aceite de oliva, el vino tinto, el brócoli, la soja etc. Los alimentos funcionales son normalmente empleados en mezclas nutricionales y en la industria farmacéutica. Del mismo modo que algunos alimentos pueden ser clasificados como alimento funcional, también se clasifican así a algunos suplementos nutricionales, como por ejemplo ácidos grasos como los omega-3 derivados del aceite de pescado y de algunos vegetales o los antioxidantes y vitaminas.In the present invention it is understood as "functional food", a food that has an effect beneficial on health. Similarly, the term food Functional can be applied to extracts or chemical compounds obtained from common foods. Examples of foods to which they attribute functional properties to them are olive oil, the red wine, broccoli, soybeans etc. Functional foods are normally used in nutritional mixtures and industry Pharmaceutical In the same way that some foods can be classified as functional food, they are also classified as some nutritional supplements, such as fatty acids such as omega-3 derived from fish oil and of some vegetables or antioxidants and vitamins.
En la presente invención se entiende como "cosmético" a aquellas preparaciones constituidas por sustancias naturales o sintéticos o sus mezclas, de uso externo en las diversas partes del cuerpo humano: piel, sistema capilar, uñas, labios, órganos genitales externos, dientes y membranas mucosas de la cavidad oral, con el objeto exclusivo o principal de higienizarlas, perfumarlas, cambiarles su apariencia, protegerlos o mantenerlos en buen estado y /o corregir olores corporales.In the present invention it is understood as "cosmetic" to those preparations constituted by natural or synthetic substances or mixtures thereof, for external use in the various parts of the human body: skin, hair system, nails, lips, external genital organs, teeth and mucous membranes of the oral cavity, with the exclusive or main purpose of sanitize them, perfume them, change their appearance, protect them or keep them in good condition and / or correct body odors.
A lo largo de la descripción y las reivindicaciones la palabra "comprende" y sus variantes no pretenden excluir otras características técnicas, componentes o pasos. Para los expertos en la materia, otros objetos, ventajas y características de la invención se desprenderán en parte de la descripción y en parte de la práctica de la invención. Los siguientes ejemplos se proporcionan a modo de ilustración, y no se pretende que sean limitativos de la presente invención.Throughout the description and the claims the word "comprises" and its variants not they intend to exclude other technical characteristics, components or Steps. For experts in the field, other objects, advantages and features of the invention will be apparent in part from the description and in part of the practice of the invention. The The following examples are provided by way of illustration, and are not It is intended to be limiting of the present invention.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
A continuación se describen algunos ejemplos de aplicación del procedimiento descrito que se proporcionan a modo de ilustración y no tienen el propósito de limitar la presente invención.Some examples of application of the described procedure that are provided by way of illustration and are not intended to limit this invention.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
La trans-feruloilnoradrenalina se sintetizó químicamente en el laboratorio con el fin de verificar su identidad y proceder al estudio de sus propiedades, se sintetizó mediante la reacción de los ácidos p-cumárico (ácido 4-hidroxicinámico) y ferúlico (ácido 4-hidroxi-3-metoxicinámico) con noradrenalina (2-[3,4-dihidroxifenil]-2-hidroxietilamina), en presencia del catalizador N, N'-diciclohexilcarbodiimida (DCC), siguiendo el método descrito por Tanaka H, Takeshi N, Kazuhiko I, Kazuo I (1989) A phenolic amide from Actinodaphne longifolia. Phytochemistry 289: 2516-2517. Se mezclaron 0,5 nmol del correspondiente ácido y 0,65 nmol de la correspondiente amina, en 20 mL de dimetilformamida (DMF). A continuación se añadió una solución del catalizador DCC (0,8 nmol/5 mL de DFM). La reacción se dejó toda la noche a temperatura ambiente. Después de eliminar los disolventes, se realizó una extracción líquido-líquido con agua y acetato de etilo. La fase orgánica se secó con Na_{2}SO_{4} anhidro, se filtró y se evaporó hasta la obtención de un aceite viscoso. Dicho aceite se purificó hasta el aislamiento de la correspondiente amida, mediante una columna de silicagel flash (Merck, 0,040-0,063 mm), utilizando como fase móvil una mezcla de di el oro metan o/acetato de etilo (1:1).The trans-feruloylnoradrenaline was chemically synthesized in the laboratory in order to verify its identity and proceed to the study of its properties, it was synthesized by the reaction of p- fumaric (4-hydroxycinnamic acid) and ferulic (4-hydroxy-acid 3-methoxycinnamic) with norepinephrine (2- [3,4-dihydroxyphenyl] -2-hydroxyethylamine), in the presence of the catalyst N, N'-dicyclohexylcarbodiimide (DCC), following the method described by Tanaka H, Takeshi N, Kazuhiko I, Kazuo I (1989) A phenolic amide from Actinodaphne longifolia. Phytochemistry 289: 2516-2517 . 0.5 nmol of the corresponding acid and 0.65 nmol of the corresponding amine were mixed in 20 mL of dimethylformamide (DMF). A solution of the DCC catalyst (0.8 nmol / 5 mL of DFM) was then added. The reaction was left overnight at room temperature. After removing the solvents, a liquid-liquid extraction with water and ethyl acetate was performed. The organic phase was dried with anhydrous Na2SO4, filtered and evaporated until a viscous oil was obtained. Said oil was purified until the corresponding amide was isolated, by means of a flash silica gel column (Merck, 0.040-0.063 mm), using as a mobile phase a mixture of the gold methane or / ethyl acetate (1: 1).
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
La caracterización estructural de la trans-FNA se realizó usando los siguientes equipos:The structural characterization of the trans -FNA was performed using the following equipment:
La rotación óptica se midió con un polarímetro digital Jasco DIP370. Los espectros UV se obtuvieron usando un espectrofotómetro Shimadzu UV-2101 PC. Los espectros de RMN de ^{1}H y ^{13}C, así como los espectros de RMN de 2D ^{1}H-^{1}H COSY, HSQC y HMBC RMN se realizaron en un espectrómetro RMN Bruker AV300 MHz. La multiplicidad de las señales del ^{13}C se asignó mediante experimentos DEPT realizados en el mismo. Los datos de masas de alta resolución se obtuvieron mediante un espectrómetro MicromassQ-TOFMicro acoplado a un UPLC-PDA Waters Acquity.Optical rotation was measured with a polarimeter. Jasco DIP370 digital. UV spectra were obtained using a Shimadzu UV-2101 PC spectrophotometer. The 1 H and 13 C NMR spectra, as well as the spectra of 1 H NMR - 1 H COZY, HSQC and HMBC NMR are performed on a Bruker AV300 MHz NMR spectrometer. The multiplicity of the 13 C signals was assigned by DEPT experiments performed on it. High mass data resolution were obtained using a spectrometer MicromassQ-TOFMicro coupled to a UPLC-PDA Waters Acquity.
Compuesto 2, trans-FNA: Polvo blanco; [\alpha]^{25}_{D} +40.9º (c 1.1, MeOH); UV (MeOH) \lambda_{max} (log \varepsilon) 290 (1.10), 318 (1.25) nm; ^{1}H NMR (MeOH-d_{4}, 300 MHz); \delta 7.45 (1H, d, J=15.7, H-7), 7.12 (1H, d, J=1.8, H-2), 7.02 (1H, dd, J=8.1, 1.8, H-6), 6.85 (1H, d, J=1.5, H-2'), 6.79 (1H, d, J=8.1, H-5), 6.76 (1H, d, J= 8.2, H-5'), 6.73 (1H, dd, J= 8.2, 1.5, H-6'), 6.46 (1H, d, J=15.7, H-8), 4.65 (1H, dd, J=7.7, 4.9, H-7'), 3.88 (3H, s, OCH_{3}), 3.52 (1H, dd, J=13.5, 4.9, H8'a), 3.42 (1H, dd, J=13.5, 7.7, H8'b); ^{13}C NMR (MeOH-d_{4} 75 MHz); \delta 169.9 (C, C-9), 149.9 (C, C-4), 149.3 (C, C-3), 146.9 (C, C-3'), 146.3 (C, C-4'), 142.3 (CH, C-7), 135.6 (C, C-1'), 128.3 (C, C-1), 123.3 (CH, C-6), 118.8 (CH, C-8), 118.7 (CH, C-6'), 116.5 (CH, C-5), 116.2 (CH, C-5'), 114.5 (CH, C-2'), 111.6 (CH, C-2), 73.6 (CH, C-7'), 55.2 (OCH_{3}), 47.2 (CH_{2}, C-8'); HRESIMS m/z 344.1118 [M-H]^{-} (calculado para C_{18}H_{18}NO_{6}, 344.1134).Compound 2, trans -FNA: White powder; [α] 25 D + 40.9 ° (c 1.1, MeOH); UV (MeOH) λ max (log ε) 290 (1.10), 318 (1.25) nm; 1 H NMR (MeOH- d 4, 300 MHz); δ 7.45 (1H, d, J = 15.7, H-7), 7.12 (1H, d, J = 1.8, H-2), 7.02 (1H, dd, J = 8.1, 1.8, H-6), 6.85 (1H, d, J = 1.5, H-2 '), 6.79 (1H, d, J = 8.1, H-5), 6.76 (1H, d, J = 8.2, H-5'), 6.73 (1H, dd, J = 8.2, 1.5, H-6 '), 6.46 (1H, d, J = 15.7, H-8), 4.65 (1H, dd, J = 7.7, 4.9, H-7'), 3.88 (3H , s, OCH 3), 3.52 (1H, dd, J = 13.5, 4.9, H8'a), 3.42 (1H, dd, J = 13.5, 7.7, H8'b); 13 C NMR (MeOH- d 4 75 MHz); δ 169.9 (C, C-9), 149.9 (C, C-4), 149.3 (C, C-3), 146.9 (C, C-3 '), 146.3 (C, C-4'), 142.3 (CH, C-7), 135.6 (C, C-1 '), 128.3 (C, C-1), 123.3 (CH, C-6), 118.8 (CH, C-8), 118.7 (CH, C -6 '), 116.5 (CH, C-5), 116.2 (CH, C-5'), 114.5 (CH, C-2 '), 111.6 (CH, C-2), 73.6 (CH, C-7 '), 55.2 (OCH 3), 47.2 (CH 2, C-8'); HRESIMS m / z 344.1118 [MH] - (calculated for C 18 H 18 NO 6, 344.1134).
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
En el presente ejemplo de realización se ha estudiado la capacidad antioxidante de trans HCAA, formadas en este caso por los ácidos p-cumárico y ferúlico con noradrenalina y octopamina. Dicha actividad antioxidante fue evaluada mediante el ensayo basado en la inactivación del radical libre estable 2,2-difenil-1-picrilhidracil (DPPH) (Hirota A, Morimitsu Y, Hojo H (1997). New antioxidative indophenol-reducing phenol compounds isolated from Mortierella sp. fungus. Bioscience Biotechnology and Biochemistry, 61: 647-650). También se evaluaron el CGA y la rutina junto a su aglicona quercetina, empleadas como moléculas de referencia, ya que su elevada actividad antioxidante ha sido probada con anterioridad (Niggeweg R, Michael AJ, Martin C (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid. Nat. Biotechnol. 22: 746-754; Nijveldt RJ, van Nood E, van Hoorn D EC, Boelens PG, van Norren K, van Leeuwen PAM (2001) Flavonoids: a review of probable mechanisms of action and potential applications American Journal of Clinical Nutrition 744: 418-425). La tabla 1 muestra los resultados obtenidos. Para la realización del ensayo se mezclaron 2 mL de una disolución etanólica del compuesto ensayado a diferentes concentraciones, con 1mL de una disolución de DPPH 0,5 mM (disuelto en etanol) y 2 mL de acetato sódico 0,1 M (pH 5.5). Después de mantener la mezcla en agitación a 25ºC durante 30 min, se realizó una medida de la absorbancia a 517 nm en un espectrofotómetro JENWAY 6305 (Alfaro C, Urios A, González MC, Moya P, Blanco M (2003) Screening for metabolites from Penicillium novae-zeelandiae displaying radical-scavening activity and oxidative mutagenicity: isolation of gentisyl alcohol. Mutat. Res. 539: 187-194). La capacidad de inactivación del radical libre DPPH por parte de cada producto ensayado, se expresó como la concentración de producto necesaria para reducir al 50% la absorbancia del DPPH a 517 nm (ED_{50}). Como control positivo se utilizó hidroxitolueno butilado (BHT), un importante antioxidante sintético (E-321) utilizado como aditivo alimentario. Los datos obtenidos representan la media de tres experimentos independientes.In the present embodiment, the antioxidant capacity of trans HCAA has been studied, formed in this case by p- fumaric and ferulic acids with norepinephrine and octopamine. Said antioxidant activity was evaluated by the assay based on the inactivation of the stable free radical 2,2-diphenyl-1-picrylhydracil (DPPH) ( Hirota A, Morimitsu Y, Hojo H (1997). New antioxidative indophenol-reducing phenol compounds isolated from Mortierella sp. Fungus, Bioscience Biotechnology and Biochemistry, 61: 647-650 ). The CGA and the routine were also evaluated together with their aglycone quercetin, used as reference molecules, since their high antioxidant activity has been previously tested ( Niggeweg R, Michael AJ, Martin C (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid Nat. Biotechnol. 22: 746-754; Nijveldt RJ, van Nood E, van Hoorn D EC, Boelens PG, van Norren K, van Leeuwen PAM (2001) Flavonoids: a review of probable mechanisms of action and potential applications American Journal of Clinical Nutrition 744: 418-425 ). Table 1 shows the results obtained. To perform the test, 2 mL of an ethanolic solution of the compound tested at different concentrations was mixed with 1 mL of a 0.5 mM DPPH solution (dissolved in ethanol) and 2 mL of 0.1 M sodium acetate (pH 5.5) . After keeping the mixture under stirring at 25 ° C for 30 min, a measurement of the absorbance at 517 nm was performed on a JENWAY 6305 spectrophotometer ( Alfaro C, Urios A, González MC, Moya P, Blanco M (2003) Screening for metabolites from Penicillium novae-zeelandiae displaying radical-scavening activity and oxidative mutagenicity: isolation of gentisyl alcohol. Mutat. Res. 539: 187-194 ). The inactivation capacity of the DPPH free radical by each product tested was expressed as the concentration of the product necessary to reduce the absorbance of DPPH to 50% at 517 nm (ED 50). As a positive control, butylated hydroxytoluene (BHT), an important synthetic antioxidant (E-321) used as a food additive was used. The data obtained represent the average of three independent experiments.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
Los valores de la tabla representan la concentración de compuesto (\muM) necesaria para reducir a la mitad la absorbancia del DPPH (ED_{50}). Valores menores de ED_{50} indican mayor poder antioxidante. Como control del experimento se utilizó el antioxidante comercial BHT.The values in the table represent the compound concentration (µM) necessary to reduce the half the absorbance of DPPH (ED 50). Values less than ED 50 indicate greater antioxidant power. As control of experiment the commercial antioxidant BHT was used.
Comparando los valores obtenidos para cada compuesto con el control se observa, efectivamente, que el CGA y la rutina poseen elevada actividad antioxidante. En cuanto a las HCAA, hay que destacar las amidas derivadas de la noradrenalina (trans-p-CNA y trans-FNA), pues muestran una capacidad antioxidante superior al control. Concretamente, la trans-FNA presenta un valor muy bajo de ED_{50}, lo que supone una actividad antioxidante muy elevada, aproximadamente 8 veces mayor al antioxidante comercial BHT utilizado como referencia. Una vez observada la gran actividad antioxidante de la trans-FNA (ED_{50} = 7,92 \pm 0,01), se comparó frente a la de otros potentes y conocidos antioxidantes de origen natural como el ácido gentísico, el ácido ascórbico (vitamina C), el tocoferol (vitamina E) y el resveratrol (antioxidante presente en el vino), mostrando una eficacia muy superior.Comparing the values obtained for each compound with the control, it is observed that the CGA and the routine have high antioxidant activity. Regarding HCAA, the amides derived from norepinephrine ( trans-p -CNA and trans -FNA) should be noted, since they show an antioxidant capacity superior to the control. Specifically, trans- FNA has a very low value of ED 50, which is a very high antioxidant activity, approximately 8 times higher than the commercial BHT antioxidant used as a reference. Once the great antioxidant activity of trans- FNA (ED 50 = 7.92 ± 0.01) was observed, it was compared against that of other potent and known antioxidants of natural origin such as gentisic acid, ascorbic acid (vitamin C), tocopherol (vitamin E) and resveratrol (antioxidant present in wine), showing a much higher efficacy.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
\newpage\ newpage
Los valores de la tabla representan la concentración de compuesto (\muM) necesaria para reducir a la mitad la absorbancia del DPPH (ED_{50}), así que valores menores de ED_{50} indican mayor poder antioxidante.The values in the table represent the compound concentration (µM) necessary to reduce the half the absorbance of DPPH (ED 50), so lower values of ED 50 indicate greater antioxidant power.
Como se puede observar en la tabla 2, la capacidad antioxidante de la trans-FNA + supera en más de 4 veces la de la vitamina E, comúnmente utilizada como conservante en la industria alimentaria, 10 veces superior a la de la vitamina C y supera en más de un orden de magnitud al conocido antioxidante del vino, resveratrol.As can be seen in Table 2, the antioxidant capacity of trans -FNA + exceeds more than 4 times that of vitamin E, commonly used as a preservative in the food industry, 10 times higher than that of vitamin C and exceeds in more than one order of magnitude to the known antioxidant of wine, resveratrol.
Claims (21)
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
- a.to.
- dejar reaccionar toda la noche a temperatura ambiente;leave react overnight at room temperature;
- b.b.
- eliminar los disolventes;remove solvents;
- c.C.
- realizar una extracción líquido-líquido con agua y acetato de etilo;perform an extraction liquid-liquid with water and acetate ethyl;
- d.d.
- secar la fase orgánica con Na_{2}SO_{4} anhidro;dry off the organic phase with anhydrous Na2SO4;
- e.and.
- filtrar y evaporar hasta la obtención de un aceite viscoso;filter and evaporate until obtaining of a viscous oil;
- f.F.
- purificar el aceite hasta el aislamiento de la trans-feruloilnoradrenalina, mediante una columna de silicagel flash, utilizando como fase móvil una mezcla de diclorometano/acetato de etilo (1:1); ypurify the oil until trans-feruloylnoradrenaline isolation, using a flash silica gel column, using as mobile phase a dichloromethane / ethyl acetate mixture (1: 1); Y
- g.g.
- aislamiento mediante HPLC acoplado a un detector PDA en una columna preparativa de fase reversa C18 SymmetryPrep 7 \mum (19 x 150 mm, Waters) a temperatura ambiente y en condiciones isocráticas usando una mezcla de MeOH y 1% ácido acético (25:75) a un flujo de 10 ml/min.HPLC isolation coupled to a PDA detector in a C18 reverse phase preparative column SymmetryPrep 7 \ mum (19 x 150 mm, Waters) at room temperature and under isocratic conditions using a mixture of MeOH and 1% acid acetic (25:75) at a flow of 10 ml / min.
\vskip1.000000\baselineskip\ vskip1.000000 \ baselineskip
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES201030693A ES2369825B1 (en) | 2010-05-11 | 2010-05-11 | COMPOSED WITH ANTIOXIDANT ACTIVITY. |
| PCT/ES2011/070269 WO2011141598A1 (en) | 2010-05-11 | 2011-04-15 | Compound with antioxidant activity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES201030693A ES2369825B1 (en) | 2010-05-11 | 2010-05-11 | COMPOSED WITH ANTIOXIDANT ACTIVITY. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2369825A1 true ES2369825A1 (en) | 2011-12-07 |
| ES2369825B1 ES2369825B1 (en) | 2012-10-23 |
Family
ID=44913988
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES201030693A Withdrawn - After Issue ES2369825B1 (en) | 2010-05-11 | 2010-05-11 | COMPOSED WITH ANTIOXIDANT ACTIVITY. |
Country Status (2)
| Country | Link |
|---|---|
| ES (1) | ES2369825B1 (en) |
| WO (1) | WO2011141598A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070183996A1 (en) * | 2005-11-08 | 2007-08-09 | Sabrina Okombi | Para-coumaric acid or para-hydroxycinnamic acid derivatives and their use in cosmetic or dermatological compositions |
-
2010
- 2010-05-11 ES ES201030693A patent/ES2369825B1/en not_active Withdrawn - After Issue
-
2011
- 2011-04-15 WO PCT/ES2011/070269 patent/WO2011141598A1/en active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070183996A1 (en) * | 2005-11-08 | 2007-08-09 | Sabrina Okombi | Para-coumaric acid or para-hydroxycinnamic acid derivatives and their use in cosmetic or dermatological compositions |
Non-Patent Citations (3)
| Title |
|---|
| KÄHKÖNEN, M.P. ET AL.:"Antioxidant activity of plant extracts containing phenolic compound". J. Agric. Food. Chem. 1999, vol. 47, páginas 3954-3962, todo el documento * |
| KORKINA, L.G.:"Phenylpropanoids as naturally occurring antioxidants: from plant defense to human health". Cellular and Molecular Biology, 2007, vol. 53, nº 1, páginas 15-25, todo el documento * |
| ZACARES, L. ET AL: "Induction of p-coumaroyldopamine and feruloyldopamine, two novel metabolites, in tomato by the bacterial pathogen pseudomonas syringae". Molecular Plant-Microbe interactions, 2007, vol. 20, nº 11, páginas 1439-1448, tabla1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2011141598A1 (en) | 2011-11-17 |
| ES2369825B1 (en) | 2012-10-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mgbeahuruike et al. | Bioactive compounds from medicinal plants: Focus on Piper species | |
| Borges-Argáez et al. | In vitro evaluation of anthraquinones from Aloe vera (Aloe barbadensis Miller) roots and several derivatives against strains of influenza virus | |
| Chen et al. | Cytotoxic prenylflavanones from Taiwanese propolis | |
| Xu et al. | Naturally occurring arbutin derivatives and their bioactivities | |
| Mahendran et al. | Synthesis and evaluation of analgesic and anti-inflammatory activities of most active free radical scavenging derivatives of Embelin—A Structure–Activity relationship | |
| KR100892596B1 (en) | Biphenyl Diol Derivatives and Compositions Comprising the Same as an Active Ingredient | |
| Rios | Natural alkamides: pharmacology, chemistry and distribution | |
| ES2909403T3 (en) | Prenylated hydroxystilbenes | |
| Kumar et al. | Amides from plants: structures and biological importance | |
| Cai et al. | Bone-targeting glycol and NSAIDS ester prodrugs of rhein: synthesis, hydroxyapatite affinity, stability, anti-inflammatory, ulcerogenicity index and pharmacokinetics studies | |
| Wang et al. | Antifeedant activities of methanol extracts of four Zanthoxylum species and benzophenanthridines from stem bark of Zanthoxylum schinifolium against Tribolium castaneum | |
| Liang et al. | Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids | |
| Hussein et al. | Synthesis of cinnamyl and caffeoyl derivatives of Cucurbitacin-Eglycoside Isolated from Citrullus colocynthis fruits and their structures antioxidant and anti-inflammatory activities relationship | |
| KR101877932B1 (en) | Composition for controlling nematode comprising grammicin compound as effective component and uses thereof | |
| Queiroz et al. | New and bioactive aromatic compounds from Zanthoxylum zanthoxyloides | |
| Montenegro et al. | Isolation and identification of compounds from the resinous exudate of Escallonia illinita Presl. and their anti-oomycete activity | |
| ES2369825B1 (en) | COMPOSED WITH ANTIOXIDANT ACTIVITY. | |
| Sandjo et al. | Ceramides, cerebrosides, and related long chains containing derivatives from the medicinal plants of Africa | |
| Manivannan et al. | Anti-microbial and anti-inflammatory flavonoid constituents from the leaves of Lawsonia inermis | |
| Ibrahim et al. | Cytotoxicity study on Maerua pseudopetalosa (Glig and Bened.) De Wolf tuber fractions | |
| Kamto et al. | An aromatic amide C-glycoside and a cyclitol derivative from stem barks of Piper guineense Schum and Thonn (Piperaceae) | |
| RO122254B1 (en) | Process for preparing pure esculetin from aesculus hippocastanum bark or fraxinus species bark | |
| Tavan et al. | Biochemical changes and enhanced accumulation of phenolic compounds in cell culture of Perilla frutescens (L.) by nano-chemical elicitation | |
| Begum et al. | Biologically active compounds from Leucas lavandulaefolia | |
| Maryono et al. | Usnic acid derivate from Usnea sp. and bioactivity against arthemia salina leach |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG2A | Definitive protection |
Ref document number: 2369825 Country of ref document: ES Kind code of ref document: B1 Effective date: 20121023 |
|
| FA2A | Application withdrawn |
Effective date: 20130422 |