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Design, synthesis, and biological evaluation of chalcone-linked thiazole-imidazopyridine derivatives as anticancer agents

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Abstract

A novel library of chalcone linked thiazole-imidazopyridine (12a–j) derivatives were designed, synthesized, and their structures were characterized by 1H NMR, 13C NMR and mass spectral studies. Further, all compounds were tested for their anticancer effects on four human cancer cell lines including MCF-7 (breast carcinoma), A549 (lung carcinoma), DU-145 (prostate carcinoma) and MDA MB-231 (breast carcinoma) by employing MTT method, using etoposide as the positive control. Among them, compound 12b displayed more potent anticancer activity against four cancer cell lines when compared to the positive control.

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References

  • Agarwal M, Singh V, Sharma SC, Sharma P, Ansari MdY, Jadav SS, Yasmin S, Sreenivasulu R, Hassan MdH (2016) Design and synthesis of new 2,5-disubstituted 1,3,4-oxadiazole analogues as anticancer agents. Med Chem Res 25:2289–2303

    CAS  Google Scholar 

  • Ahsan MJ, Choudhary K, Jadav SS, Yasmin S, Ansari MY, Sreenivasulu R (2015) Synthesis, antiproliferative activity and molecular docking studies of curcumin analogues bearing pyrazole ring. Med Chem Res 24:4166–4180

    CAS  Google Scholar 

  • Al-Tel TH, Al-Qawasmeh RA, Zaarour R (2011) Design, synthesis and in vitro antimicrobial evaluation of novel imidazo[1,2-a]pyridine and imidazo[2,1-b][1,3]benzothiazole motifs. Eur J Med Chem 46:1874–1881

    CAS  PubMed  Google Scholar 

  • Bukowski L, Kaliszan R (1991) Imidazo[4,5-b]pyridine derivatives of potential tuberculostatic activity, II: synthesis and bioactivity of designed and some other 2-cyanomethylimidazo[4,5-b]pyridine derivatives. Arch Pharm 9:537–542

    Google Scholar 

  • Byth KF, Geh C, Forder CL, Oakes SE, Thomas AP (2006) The cellular phenotype of AZ703, a novel selective imidazo[1,2-a]pyridine cyclin-dependent kinase inhibitor. Mol Cancer Ther 5:655–664

    CAS  PubMed  Google Scholar 

  • Cheenpracha S, Karalai C, Ponglimanont C, Subhadhirasakul S, Tewtrakul S (2006) Anti-HIV-1 protease activity of compounds from Boesenbergia pandurata. Bioorg Med Chem 14:1710–1714

    CAS  PubMed  Google Scholar 

  • Clayton PE, Banerjee I, Murray PG, Renehan AG (2011) Growth hormone, the insulin-like-growth factor axis, insulin and cancer risk. Nat Rev Endocrinol 7:11–24

    CAS  PubMed  Google Scholar 

  • Clemens MR (1991) Free radicals in chemical carcinogenesis. KlinWochenschr 69:1123–1134

    CAS  Google Scholar 

  • Dimmock JR, Kandepu NM, Hetherinqton M, Quail JW, Pugazhenthi U, Sudom AM, Chamankhah M, Rose P, Pass E, Allen TM, Halleran S, Szydlowski J, Mutus B, Tannous M, Manavathu EK, Myers TG, Clercq ED, Balzarini J (1998) Cytotoxic activities of mannich bases of chalcones and related compounds. J Med Chem 41:1014–1026

    CAS  PubMed  Google Scholar 

  • Ducki S, Forrest R, Hadfield JA, Kendall A, Lawerence NJ, McGrown AT, Rennison D (1998) Antileishmanial chalcones: statistical design, synthesis, and three-dimensional quantitative structure−activity relationship analysis. Bioorg Med Chem Lett 8:1051–1056

    CAS  PubMed  Google Scholar 

  • Durgesh R, Sreenivasulu R, Srinivasarao P, Raju RR (2018a) Synthesis and anti-tumor evaluation of novel 5-bromo indole-aryl ketohydrazide-hydrazone analogues. Asian J Chem 30:1201–1204

    Google Scholar 

  • Durgesh R, Sreenivasulu R, Srinivasarao P, Raju RR (2018b) Synthesis and anticancer evaluation of indazole-aryl hydrazide-hydrazone derivatives. J Ind Chem Soc 95:433–438

    Google Scholar 

  • Durgesh R, Sreenivasulu R, Raju RR (2018c) Synthesis and anti-tumor evaluation of Indole-substituted Indole fused keto hydrazide-hydrazones. J Pharm Res 12:42–46

    Google Scholar 

  • ElHady AK, Abdel-Halim, Abadi MAH, Engel M (2017) Development of selective Clk1 and -4 inhibitors for cellular depletion of cancer-relevant proteins. J Med Chem 60:5377–5391

    CAS  PubMed  Google Scholar 

  • Fu Y, Hsieh TC, Guo J, Kunicki J, Lee MYWT, Darzynkiewicz Z, Wu JM (2004) Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells. Biochem Biophys Res Commun 322:263–270

    CAS  PubMed  Google Scholar 

  • Furman C, Lebeau J, Fruchart JC, Bernier JL, Duiez P, Cotelle N, Teissier E (2001) Di-tert-butylhydroxylated flavonoids protect endothelial cells against oxidized LDL-induced cytotoxicity. J Biochem Mol Toxicol 15:270–278

    CAS  PubMed  Google Scholar 

  • Go ML, Wu X, Liu XL (2005) Chalcones: an update on cytotoxic and chemo protective properties. Curr Med Chem 12:481–499

    CAS  PubMed  Google Scholar 

  • Gudmundsson KS, Williams JD, Drach JC, Townsend LB (2003) Synthesis and antiviral activity of novel erythrofuranosyl imidazo[1,2-a]pyridine C-nucleosides constructed via palladium coupling of iodoimidazo[1,2-a]pyridines and dihydrofuran. J Med Chem 46:1449–1455

    CAS  PubMed  Google Scholar 

  • Gueiffier A, Mavel S, Lhassani M, Elhakmaoui A, Snoeck R, Andrei G, Chavignon O, Teulade JC, Witvrouw M, Balzarini J, De Clercq E, Chapat JP (1998) Synthesis of imidazo[1,2-a]pyridines as antiviral agents. J Med Chem 41:5108–5112

    CAS  PubMed  Google Scholar 

  • Harrison TS, Keating GM (2005) Zolpidem: a review of its use in the management of insomnia. CNS Drugs 19:65–89

    CAS  Google Scholar 

  • Hatti I, Sreenivasulu R, Jadav SS, Ahsan MJ, Raju RR (2015a) Synthesis and biological evaluation of 1,3,4-oxadiazole linked bis indole derivatives as anticancer agents. Monatsh Chem 146:1699–1705

    CAS  Google Scholar 

  • Hatti I, Sreenivasulu R, Jadav SS, Jayaprakash V, Kumar CG, Raju RR (2015b) Synthesis, cytotoxic activity and docking studies of new 4 – aza podophyllotoxin derivatives. Med Chem Res 24:3305–3313. https://www.rcsb.org/5X8I

  • John R, Ross H (2010) The global economic cost of cancer. American Cancer Society, Atlanta

  • Kamal A, Kumar GB, Nayak VL, Reddy VS, Shaik AB, Rajender K, Reddy MK (2015) Design, synthesis and biological evaluation of imidazopyridine/imidazopyrimidine-benzimidazole conjugates as potential anticancer agents. Med Chem Commun 6:606–612

    CAS  Google Scholar 

  • Kamal A, Reddy JS, Ramaiah MJ, Dastagiri D, Bharathi EV, Sagar MVP, Pushpavalli SNCVL, Ray P, Pal-Bhadra M (2010) Design, synthesis and biological evaluation of imidazopyridine/pyrimidine-chalcone derivatives as potential anticancer agents. Med Chem Commun 1:355–360

    CAS  Google Scholar 

  • Kercher T, Rao C, Bencsik JR, Josey JA (2007) Diversification of the three-component coupling of 2-aminoheterocycles, aldehydes, and isonitriles: efficient parallel synthesis of a diverse and druglike library of imidazo- and tetrahydroimidazo[1.2-a]heterocycles. J Comb Chem 9:1177–1187

    CAS  PubMed  Google Scholar 

  • Lacerda RB, de Lima CK, da Silva LL, Romeiro NC, Miranda AL, Barreiro EJ, Fraga CA (2009) Discovery of novel analgesic and anti-inflammatory 3-arylamine-imidazo[1,2a]pyridine symbiotic prototypes. Bioorg Med Chem 17:74–84

    CAS  PubMed  Google Scholar 

  • Lahtchev KL, Batovska DI, Parushev SP, Ubiyvovk VM, Sibirny AA (2008) Antifungal activity of chalcones: a mechanistic study using various yeast strains. Eur J Med Chem 43:2220–2228

    CAS  PubMed  Google Scholar 

  • Lancel M, Steiger A (1999) Sleep and its modulation by drugs that affect GABA, receptor function. Angew Chem Int Ed 38:2852–2864

    CAS  Google Scholar 

  • Langer SZ, Arbilla S, Benavides J, Scatton B (1990) Zolpidem and alpidem: two imidazopyridines with selectivity for omega 1- and omega 3-receptor subtypes. Adv Biochem Psychopharmacol 46:61–72

    CAS  PubMed  Google Scholar 

  • Larsen M, Kromannn H, Kharazmi A, Nielsen SF (2005) Conformationally restricted anti plasmodial chalcones. Bioorg Med Chem Lett 15:4858–4861

    CAS  PubMed  Google Scholar 

  • Liaras K, Geronikaki A, Glamoclija J, Ciric A, Sokovic M (2011) Thiazole-based chalcones as potent antimicrobial agents. Synthesis and biological evaluation. Bioorg Med Chem Lett 19:3135–3140

    CAS  Google Scholar 

  • Lin YM, Zhou LM, Flavin MT, Nie W, Chen FC (2002) Chalcones and flavonoids as anti-tuberculosis agents. Bioorg Med Chem 10:2795–2802

    CAS  PubMed  Google Scholar 

  • Madhavi S, Sreenivasulu R, Ansari MdY, Ahsan MJ, Raju RR (2016) Synthesis, biological evaluation and molecular docking studies of pyridine incorporated chalcone derivatives as anticancer agents. Lett Org Chem 13:682–692

    CAS  Google Scholar 

  • Madhavi S, Sreenivasulu R, Jyotsna Y, Raju RR (2017a) Synthesis of chalcone incorporated quinazoline derivatives as anticancer agents. Saudi Pharm J 25:275–279

    PubMed  Google Scholar 

  • Madhavi S, Sreenivasulu R, Raju RR (2017b) Synthesis and biological evaluation of oxadiazole incorporated ellipticine derivatives as anticancer agents. Monatsh Chem 148:933–938

    CAS  Google Scholar 

  • Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    CAS  Google Scholar 

  • Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (2003) NF-kappa B functions in synaptic signaling and behaviour. Nat Neurosci 6:1072–1078

    CAS  PubMed  Google Scholar 

  • Modzelewska A, Pettit C, Achanta G, Davidson NE, Huang P, Khan SR (2006) Anticancer activities of novel chalcone and bis-chalcone derivatives. Bioorg Med Chem 14:3491–3495

    CAS  PubMed  Google Scholar 

  • Murthy IS, Sreenivasulu R, Alluraiah G, Raju RR (2019) Design, synthesis and anticancer evaluation of 1,2,3-triazole linked 1,2-isoxazole - imidazo[4,5-b]pyridine derivatives. Russian J Gen Chem 89:1718–1723

    CAS  Google Scholar 

  • Nielsen SF, Christensen SB, Cruciani G, Kharazmi A, Liljefors T (1998) Antileishmanial chalcones: statistical design, synthesis, and three-dimensional quantitative structure−activity relationship analysis. J Med Chem 41:4819–4832

    CAS  PubMed  Google Scholar 

  • Nowakowska Z (2007) A review of anti-infective and anti-inflammatory chalcones. Eur J Med Chem 42:125–137

    CAS  PubMed  Google Scholar 

  • Park SK, Cho LY, Yang JJ, Park B, Chang SH, Lee KS, Kim H, Yoo KY, Lee CT (2010) Lung cancer risk and cigarette smoking, lung tuberculosis according to histologic type and gender in a population based case-control study. Lung Cancer 68:20–26

    PubMed  Google Scholar 

  • Porta C, Riboldi E, Sica A (2011) Mechanisms linking pathogens-associated inflammation and cancer. Cancer Lett 305:250–262

    CAS  PubMed  Google Scholar 

  • Pragathi YJ, Sreenivasulu R, Veronica D, Madhavi S, Raju RR (2019) Design, synthesis and biological evaluation of novel 2-(4-aryl-substituted-1H-1,2,3-triazol-1-yl)-N-(4-(2- (thiazol-2-yl)benzo[d]thiazol-6-yl)phenyl) acetamide derivatives as potent anticancer agents. Russian J Gen Chem 89:1009–1014

    CAS  Google Scholar 

  • Rao BVD, Sreenivasulu R, Rao MVB (2019) Design, synthesis, and evaluation of isoxazole-thiadiazole linked carbazole hybrids as anticancer agents. Russian J Gen Chem 89:2115–2120

    Google Scholar 

  • Reddy NB, Burra VR, Ravindranath LK, Kumar VN, Sreenivasulu R, Sadanandam P (2016a) Synthesis and biological evaluation of benzimidazole fused ellipticine derivatives as anticancer agents. Monatsh Chem 147:599–604

    Google Scholar 

  • Reddy NB, Burra VR, Ravindranath LK, Sreenivasulu R, Kumar VN (2016b) Synthesis and biological evaluation of benzoxazole fused combretastatin derivatives as anticancer agents. Monatsh Chem 147:593–598

    Google Scholar 

  • Reddy KT, Sreenivasulu R, Raju RR (2019) Synthesis and biological evaluation of 1,2,4-oxadiazole linked imidazopyrazine derivatives as anticancer agents. J Ind Chem Soc 96:1085–1090

    CAS  Google Scholar 

  • Rival Y, Grassy G, Taudon A, Ecalle R (1991) Antifungal activity in vitro of some imidazo[1,2-a]pyrimidine derivatives Activité antifongique in vitro de quelques dérivés de l’imidazo[1,2-a]pyrimidine. Eur J Med Chem 26:13–18

    CAS  Google Scholar 

  • Rojas J, Payá M, Domínguez JN, Ferrándiz ML (2003) ttCH, a selective inhibitor of inducible nitric oxide synthase expression with antiarthritic properties. Eur J Pharmacol 465:183–189

    CAS  PubMed  Google Scholar 

  • Rozmer Z, Perjési P (2016) Naturally occurring chalcones and their biological activities. Phytochem Rev 15:87–120

    CAS  Google Scholar 

  • Satyanarayana M, Tiwari P, Tripathi BK, Srivastava AK, Pratap R (2004) Synthesis and antihyperglycemic activity of chalcone based aryloxypropanolamines. Bioorg Med Chem 12:883–889

    CAS  PubMed  Google Scholar 

  • Shahinshavali S, Sreenivasulu R, Guttikonda VR, Kolli D, Rao MVB (2019) Synthesis and anticancer activity of amide derivatives of 1,2-isoxazole combined 1,2,4-thiadiazole. Russian J Gen Chem 89:324–329

    CAS  Google Scholar 

  • Spandana Z, Sreenivasulu R, Rao MVB (2018a) Design, synthesis and anticancer evaluation of carbazole fused aminopyrimidine derivatives. Lett Org Chem 16:662–667

    Google Scholar 

  • Spandana Z, Sreenivasulu R, Rekha TM, Rao MVB (2018b) Novel 1,3,4-oxadiazole fused thiadiazole derivatives: synthesis and study of anticancer activities. Lett Drug Des Discov 16:656–662

    Google Scholar 

  • Sreenivasulu R, Durgesh R, Jadav SS, Sujitha P, Kumar CG, Raju RR(2018) Synthesis,anticancer evaluation and molecular docking studies of Bis(indolyl)triazinones, Nortopsentin analogues Chem Pap 72:1369–1378

    CAS  Google Scholar 

  • Sreenivasulu R, Sujitha P, Jadav SS, Ahsan MJ, Kumar CG, Raju RR (2017) Synthesis, antitumor evaluation and molecular docking studies of Indole-Indazolyl hydrazide hydrazone derivatives. Monatsh Chem 148:305–314

    CAS  Google Scholar 

  • Sreenivasulu R, Reddy KT, Jadav SS, Sujitha P, Kumar CG, Raju RR (2019) Synthesis, antiproliferative and apoptosis induction potential activities of novel bis(indolyl) hydrazide-hydrazone derivatives. Bioorg Med Chem 27:1043–1055

    CAS  PubMed  Google Scholar 

  • Sreenivasulu R, Tej MB, Jadav SS, Sujitha P, Kumar CG, Raju RR (2020) Synthesis, anticancer evaluation and molecular docking studies of 2,5-bis(indolyl)-1,3,4-oxadiazoles, Nortopsentin analogues. J Mol Struct 1208:127875

    CAS  Google Scholar 

  • Starrett JE, Montzka TA, Crosswell AR, Cavanagh RL (1989) Synthesis and biological activity of 3-substituted imidazo[1,2-a]pyridines as antiulcer agents. J Med Chem 32:2204–2210

    CAS  PubMed  Google Scholar 

  • Subramanyam M, Sreenivasulu R, Rambabu G, Rao MVB, Rao KP (2018) Synthesis, biological evaluation and docking studies of 1,3,4-oxadiazole fused benzothiazole derivatives for anticancer drugs. Lett Drug Des Discov 15:1299–1307

    CAS  Google Scholar 

  • Suma VR, Sreenivasulu R, Subramanyam M, Rao KRM (2019) Design, synthesis and anticancer activity of amide derivatives of structurally modified combretastatin-A4. Russian J Gen Chem 89:499–504

    Google Scholar 

  • Sun QZ, Lin GF, Li LL, Jin XT, Huang LY, Zhang G, Yang W, Chen X, Xiang R, Chen C, Wei YQ, Lu GW, Yang SY (2017) Discovery of potent and selective inhibitors of Cdc2-like kinase 1 (CLK1) as a new class of autophagy inducers. J Med Chem 60:6337–6352

    CAS  PubMed  Google Scholar 

  • Temple C (1990) Antimitotic agents. Synthesis of imidazo[4,5-c]pyridine-6-ylcarbamates and imidazo[4,5-b]pyridine-5-ylcarbamates. J Med Chem 33:656–661

    CAS  PubMed  Google Scholar 

  • ChoI HG, Son JB, Kim S, Lee S, Ko E, Cho J, Kang SY, Kim SY, Park JH, Ko YK, Ryu HY, Kim ND, Kim H, Lee Y, Lee SH, Kim D, Lee SJ, Hong S, Min SH, Lee S, Choi DK, Bae JH, Hong E, Jang T, Song J, Kim S, Yoon SK (2017) Novel imidazopyridine derivative, method for preparing same, and pharmaceutical composition containing same as active ingredient for preventing or treating cancer. WO2017222285A1

  • Yakantham T, Sreenivasulu R, Raju RR (2019) Design, synthesis and anticancer evaluation of 2-(3-(4-((5-aryl-1,2,4-oxadiazol-3-yl)methoxy)phenyl)isoxazol-5-yl)-N-(3,4,5-trimethyl phenyl)thiazol-4-amine derivatives. Russ J Gen Chem 89:1485–1490

    CAS  Google Scholar 

  • Yoon G, Kang BY, Cheon SH (2007) Topoisomerase I inhibition and cytotoxicity of licochalcones A and E from Glycyrrhiza inflate. Arch Pharm Res 30:313–316

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, , GITAM Institute of Science Gandhi Institute of Technology and Management (Deemed to be University), Visakhapatnam, Andhra Pradesh, 530045, India

    Vellanki Ragha Suma & Kuppili Ram Mohan Rao

  2. Department of Chemistry, Government Degree and PG College, Bhadrachalam, Telangana, 507111, India

    Vellanki Ragha Suma

  3. Department of Chemistry, University College of Engineering (Autonomous), Jawaharlal Nehru Technological University, Kakinada, Andhra Pradesh, 533003, India

    Reddymasu Sreenivasulu

  4. Department of Chemistry, Krishna University, Machilipatnam, Andhra Pradesh, 521001, India

    Mandava Venkata Basaveswara Rao

  5. Department of Chemistry, SR and BGNR Govt. Arts and Science College (Autonomous), Khammam, Telangana, 507002, India

    Madala Subramanyam

  6. Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan, India

    Mohamed Jawed Ahsan

  7. Vishnu Institute of Pharmaceutical Education & Research (VIPER), Narsapur, Medak, Telangana, 502313, India

    Ramesh Alluri

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  1. Vellanki Ragha Suma
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  2. Reddymasu Sreenivasulu
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Suma, V.R., Sreenivasulu, R., Rao, M.V.B. et al. Design, synthesis, and biological evaluation of chalcone-linked thiazole-imidazopyridine derivatives as anticancer agents. Med Chem Res 29, 1643–1654 (2020). https://doi.org/10.1007/s00044-020-02590-9

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