Viscum cruciatum Sieb is a well-known medicinal plant in Jordan containing various secondary meta... more Viscum cruciatum Sieb is a well-known medicinal plant in Jordan containing various secondary metabolites. It has traditionally been used to treat many ailments, most notably cancer. However, there is a significant gap between scientific research and its value in traditional medicine. Aim of the work: To evaluate the antiproliferative activity of different V. cruciatum extracts against MCF-7 breast cancer cell lines and recognize the affected cell cycle phase. Besides, identifying the bioactive components present in the active extract using LC/MS technique. Also, to determine the possible mechanism of action by in silico and in-vitro study. Materials and methods: V. cruciatum was extracted using solvents with increasing polarity. The antiproliferative effects of the extracts against MCF-7 cell lines were evaluated using SRB assay. Further, flow cytometry was used to identify the inhibited phase of the cell cycle, while LC/MS-MS technique was used to analyze the chemical composition of the most active extract. After that, the putative mechanism of action was investigated through insilico docking, molecular dynamic simulation for compounds with the highest docking scores, and Western blot analysis of cyclin-dependent kinases (CDK2/4/6). Results: The chloroform/methanol 90/10 (ChMe) extract showed the most potent antiproliferative effect against MCF-7 cells (IC 50 = 23.8 μg/mL), and cell cycle arrest at the G0/G1phase. Furthermore, LC-MS/MS analysis revealed the presence of several polyphenolics belonging to the flavonoids and phenolic acids classes. Additionally, quercetin-4 ′-glucoside, 3, 5, 7-trihydroxy-4 ′-methoxy flavone, and hesperetin-7-O-neohesperidoside demonstrated the highest docking binding scores and stable complexes against CDK2 and CDK4/6. Moreover, RMSD (root-mean-square deviation), RMSF (root-mean-square fluctuation), Rg (radius of gyration), and energy analysis during molecular dynamic simulation indicated the stable binding of the studied complexes. These results were supported by Western blot analysis, which revealed the downregulation of CDK2, CDK4, and CDK6 protein expression in MCF-7 cell lines. Conclusion: These findings emphasized the potential breast anticancer activity of the V. cruciatum ChMe extract by arresting the G0/G1 phase of the cell cycle, which could be related to its flavonoid content. Moreover, the results provided experimental support for the traditional anticancer activity of V. cruciatum, and its ChMe extract might be a source of chemoprotective or chemotherapeutic isolates.
The exudate of Commicarpus grandiflorus (A. Rich.) Standl. flowering aerial parts was investigate... more The exudate of Commicarpus grandiflorus (A. Rich.) Standl. flowering aerial parts was investigated for its chemical composition. Nine compounds were isolated, five triterpenes and four methylated flavones, of which two were new natural triterpenes, 2a,3b,11a-olean-18-en-2,3,11-triol (1) and 2a,3b-olean-12-en-2,3diol-11-one (2) that were named commicarpotriol and commicarpodiol, respectively. Structural characterization was carried out using 1D, 2D NMR, and MS techniques and the antimicrobial activity of all isolates was evaluated.
Background: The genus Achillea is rich in essential oil (EO) with high chemical diversity. In thi... more Background: The genus Achillea is rich in essential oil (EO) with high chemical diversity. In this study, eight EO samples obtained from flowers and leaves of Achillea ligustica All. collected on the Mediterranean mainland and island locations were analyzed to evaluate their possible chemical diversity. Methods: Sixteen samples of EO were analyzed by GC-MS, leading to the identification of 95 compounds in the leaves and 86 compounds in the flowers; a statistical analysis was performed to determine the chemical polymorphism. Results: Monoterpenes, such as β-pinene, borneol, ɑ-terpineol and isobornyl acetate, were more abundant in the continental samples, while the insular samples were richer in 1,8-cineole. Fragranyl acetate and fragranol were detected in remarkable concentrations in sample 8. The fruits of sample 8 were then cultivated under controlled agronomic conditions, providing plants rich in these compounds (sample 9). The geographical variability influenced the EO compositio...
Arabian flora is a rich source of bioactive compounds. In this study, we investigated three aroma... more Arabian flora is a rich source of bioactive compounds. In this study, we investigated three aromatic plant species with the aim of finding valuable sources of antimicrobial agents against common pathogenic microorganisms. We focused especially on microorganisms, which cause outbreaks of infectious disease during mass gatherings and pilgrimages season in Saudi Arabia. The essential oils of three aromatic plant species were hydrodistilled from flowering aerial parts of Lavandula pubescens Decne. and Pulicaria incisa subsp. candolleana E.Gamal-Eldin, and from leaves, stems, ripe and unripe fruits of Juniperus procera Hochst. Ex Endl. They were subsequently analyzed by gas chromatography-mass spectrometry (GC-MS). The main constituents of L. pubescens were found to be carvacrol (55.7%), methyl carvacrol (13.4%), and β-bisabolene (9.1%). P. incisa subsp. Candolleana essential oil was rich in linalool (33.0%), chrysanthenone (10.3%), eugenol (8.9%), and cis-chrysanthenol (8.0%); the major...
Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russeliosid... more Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n=8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-α and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as famotidine.
In developing countries, crop deterioration is mainly caused by inappropriate storage conditions ... more In developing countries, crop deterioration is mainly caused by inappropriate storage conditions that promote insect infestation. Synthetic pesticides are associated with serious adverse effects on humans and the environment. Thus, finding alternative “green” insecticides is a very pressing need. Calotropis procera (Aiton) Dryand (Apocynaceae) growing in Saudi Arabia was selected for this purpose. LC-MS/MS analysis was applied to investigate the metabolic composition of different C. procera extracts. Particularly, C. procera latex and leaves showed a high presence of cardenolides including calactin, uscharidin, 15β-hydroxy-calactin, 16β-hydroxy-calactin, and 12β-hydroxy-calactin. The ovicidal activity of the extracts from different plant organs (flowers, leaves, branches, roots), and of the latex, against Cadra cautella (Walker) (Lepidoptera, Pyralidae) was assessed. Extracts of C. procera roots displayed the most potent activity with 50% of C. cautella eggs not hatching at 10.000 p...
Phytochemical study of the ethanolic extract of the fruits of Gleditsia aquatica and Gleditsia ca... more Phytochemical study of the ethanolic extract of the fruits of Gleditsia aquatica and Gleditsia caspica resulted in the isolation of the triterpene saponins; aquaticasaponin A (1), aquaticasaponin B (2), caspicaoside L (3) and caspicaoside M (4). Compound (1) showed good activity against methicillin resistant Staphylococcus aureus (MRSA) (IC50 =16.3 μg/mL) and Staphylococcus aureus (non-MRSA), (IC50 =12.2 μg/mL) and it expressed considerable cytotoxic activity against BT-549 (Human Ductal Carcinoma, Breast), KB (Human Epidermal Carcinoma, Oral) and SK-MEL (Human Malignant Melanoma) with IC50 values of 8.3, 10.0 and 3.3 μg/mL, respectively. Compounds (2) and (3) showed potent cytotoxicity against BT-549 with IC50 values of 5.3 and 7.3 μg/mL, and against SK-MEL with IC50 values of 4.3 and 3.1 μg/mL, respectively. Compound (4) showed good cytotoxicity against KB with IC50 value of 7.3 μg/mL. In consistent, the study of molecular determinates of cytotoxic activity of these new scaffolds ...
Evidence-Based Complementary and Alternative Medicine, 2021
4-O-Podophyllotoxin sulfamate derivatives were prepared using the natural lignan podophyllotoxin.... more 4-O-Podophyllotoxin sulfamate derivatives were prepared using the natural lignan podophyllotoxin. The prepared compounds were afforded by reacting O-sulfonyl chloride podophyllotoxin with ammonia or aminoaryl/heteroaryl motif. Biological evaluation was performed in human breast cancer (MCF7), ovarian cancer (A2780), colon adenocarcinoma (HT29), and normal lung fibroblast (MRC5) cell lines. Compound 3 exhibited potent inhibitory activity and good selectivity margin. Compounds 2, 3, and 7 exerted apoptotic effect in MCF7 cells in a dose-dependent manner. The cytotoxicity of the verified compounds was inferior to that of podophyllotoxin.
We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells a... more We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells alone or in combination treatments with quercetin. Anti-proliferative studies on A375 cells and adult human dermal fibroblasts included analyses on cell cycle distribution, caspase activity, phosphatidylserine translocation, cell morphology and Bax/Bcl-2 protein expression. Then, 2D and 3D migration of B16F10 cells were studied using scratch and Transwell assays, respectively. Ursolic acid and 3-O-acetylursolic acid have shown similar GI50 on A375 cells (26 µM vs. 32 µM, respectively) significantly increased both early and late apoptotic populations, activated caspases 3/7 (48–72 h), and enhanced Bax whilst attenuating Bcl-2 expression. Ursolic acid caused elevation of the sub-G1 population whilst its 3-acetyl derivative arrested cell cycle at S phase and induced strong morphological changes. Combination treatments showed that ursolic acid and quercetin act synergistically in migration as...
Acute myeloid leukemia (AML) is among the top four malignancies in Saudi nationals, and it is the... more Acute myeloid leukemia (AML) is among the top four malignancies in Saudi nationals, and it is the top leukemia subtype worldwide. Resistance to available AML drugs requires the identification of new targets and agents. Hsp90 is one of the emerging important targets in AML, which has a central role in the regulation of apoptosis and cell proliferation through client proteins including the growth factor receptors and cyclin dependent kinases. The objective of the first part of this study is to investigate the putative Hsp90 inhibition activity of three novel previously synthesized quinazolines, which showed HL60 cytotoxicity and VEGFR2 and EGFR kinases inhibition activities. Using surface plasmon resonance, compound 1 (HAA2020) showed better Hsp90 inhibition compared to 17-AAG, and a docking study revealed that it fits nicely into the ATPase site. The objective of the second part is to maximize the anti-leukemic activity of HAA2020, which was combined with each of the eleven standard ...
In this paper, the isolation of one new iridoid glucoside, 6β-acetoxyipolamiide (1), and thirteen... more In this paper, the isolation of one new iridoid glucoside, 6β-acetoxyipolamiide (1), and thirteen (2 – 14) known congeners from two Lamiaceae species, Stachys ocymastrum and Premna resinosa, leaf extracts is reported. The structural determination of the isolated compounds was performed by mono- and bidimensional NMR spectroscopic analysis as well as MS experiments. The isolates were assayed for their antiangiogenic activity by two in vivo models, zebrafish embryos and chick chorioallantoic membrane assays. The compounds with a significant antiangiogenic activity in both assays were β-hydroxyipolamiide (2), ipolamiide (3), and buddlejoside A5 (8). 6-O-α-l-(3″-O-p-Methoxycinnamoyl-4″-O-acetyl)rhamnopyranosyl catalpol (13) and 6-O-α-l-(2″-trans-caffeoyl)rhamnopyranosyl catalpol (6) showed the best antiangiogenic response on blood vessel growth in zebrafish embryos, whereas saccatoside (10) and 6-O-α-l-(2″-O - p-methoxycinnamoyl-3″-O-acetyl)rhamnopyranosyl catalpol (14) resulted in a st...
Angiogenesis plays a crucial role in malignant tumor progression and development. The present stu... more Angiogenesis plays a crucial role in malignant tumor progression and development. The present study aimed to identify lead plants with selective anti-angiogenic properties. A total of 26 methanolic extracts obtained from 18 plants growing in Saudi Arabia and Jordan that belong to the Lamiaceae family were screened for their cytotoxic and anti-angiogenic activities using MTT and rat aortic ring assays, respectively. Four novel extracts of Thymbra capitata (L.) Cav., Phlomis viscosa Poir, Salvia samuelssonii Rech.f., and Premna resinosa (Hochst.) Schauer were identified for their selective anti-angiogenic effects. These extracts did not exhibit cytotoxic effects on human endothelial cells (EA.hy926) indicating the involvement of indirect anti-angiogenic mechanisms. The active extracts are potential candidates for further phytochemical and mechanistic studies.
The surface extract of an accession of Psiadia punctulata (DC.) Vatke (Asteraceae) growing in Sau... more The surface extract of an accession of Psiadia punctulata (DC.) Vatke (Asteraceae) growing in Saudi Arabia was investigated for its phytochemical composition. A bio-guided investigation of the extract led to the isolation of thirteen ent-kaurane and trachylobane diterpenes and seventeen compounds previously described, including nine flavonoids and eight diterpenes. Three flavonoids and one ent-kaurane diterpene showed antimicrobial activity with MIC100 values ranging from 25 to 150 μg/ml. The extract showed antibacterial activity against Staphylococcus aureus (MIC = 180 μg/ml) and antifungal activity against Candida albicans (MIC = 130 μg/ml). The isolated 3',4',5,7-tetramethoxyflavone, at a concentration of 40 μg/ml, displayed the ability to reduce biofilm formation of S. aureus and C. albicans by 50% and 90% respectively.
Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were i... more Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, 1H-13C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showe...
The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydroch... more The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics o...
Viscum cruciatum Sieb is a well-known medicinal plant in Jordan containing various secondary meta... more Viscum cruciatum Sieb is a well-known medicinal plant in Jordan containing various secondary metabolites. It has traditionally been used to treat many ailments, most notably cancer. However, there is a significant gap between scientific research and its value in traditional medicine. Aim of the work: To evaluate the antiproliferative activity of different V. cruciatum extracts against MCF-7 breast cancer cell lines and recognize the affected cell cycle phase. Besides, identifying the bioactive components present in the active extract using LC/MS technique. Also, to determine the possible mechanism of action by in silico and in-vitro study. Materials and methods: V. cruciatum was extracted using solvents with increasing polarity. The antiproliferative effects of the extracts against MCF-7 cell lines were evaluated using SRB assay. Further, flow cytometry was used to identify the inhibited phase of the cell cycle, while LC/MS-MS technique was used to analyze the chemical composition of the most active extract. After that, the putative mechanism of action was investigated through insilico docking, molecular dynamic simulation for compounds with the highest docking scores, and Western blot analysis of cyclin-dependent kinases (CDK2/4/6). Results: The chloroform/methanol 90/10 (ChMe) extract showed the most potent antiproliferative effect against MCF-7 cells (IC 50 = 23.8 μg/mL), and cell cycle arrest at the G0/G1phase. Furthermore, LC-MS/MS analysis revealed the presence of several polyphenolics belonging to the flavonoids and phenolic acids classes. Additionally, quercetin-4 ′-glucoside, 3, 5, 7-trihydroxy-4 ′-methoxy flavone, and hesperetin-7-O-neohesperidoside demonstrated the highest docking binding scores and stable complexes against CDK2 and CDK4/6. Moreover, RMSD (root-mean-square deviation), RMSF (root-mean-square fluctuation), Rg (radius of gyration), and energy analysis during molecular dynamic simulation indicated the stable binding of the studied complexes. These results were supported by Western blot analysis, which revealed the downregulation of CDK2, CDK4, and CDK6 protein expression in MCF-7 cell lines. Conclusion: These findings emphasized the potential breast anticancer activity of the V. cruciatum ChMe extract by arresting the G0/G1 phase of the cell cycle, which could be related to its flavonoid content. Moreover, the results provided experimental support for the traditional anticancer activity of V. cruciatum, and its ChMe extract might be a source of chemoprotective or chemotherapeutic isolates.
The exudate of Commicarpus grandiflorus (A. Rich.) Standl. flowering aerial parts was investigate... more The exudate of Commicarpus grandiflorus (A. Rich.) Standl. flowering aerial parts was investigated for its chemical composition. Nine compounds were isolated, five triterpenes and four methylated flavones, of which two were new natural triterpenes, 2a,3b,11a-olean-18-en-2,3,11-triol (1) and 2a,3b-olean-12-en-2,3diol-11-one (2) that were named commicarpotriol and commicarpodiol, respectively. Structural characterization was carried out using 1D, 2D NMR, and MS techniques and the antimicrobial activity of all isolates was evaluated.
Background: The genus Achillea is rich in essential oil (EO) with high chemical diversity. In thi... more Background: The genus Achillea is rich in essential oil (EO) with high chemical diversity. In this study, eight EO samples obtained from flowers and leaves of Achillea ligustica All. collected on the Mediterranean mainland and island locations were analyzed to evaluate their possible chemical diversity. Methods: Sixteen samples of EO were analyzed by GC-MS, leading to the identification of 95 compounds in the leaves and 86 compounds in the flowers; a statistical analysis was performed to determine the chemical polymorphism. Results: Monoterpenes, such as β-pinene, borneol, ɑ-terpineol and isobornyl acetate, were more abundant in the continental samples, while the insular samples were richer in 1,8-cineole. Fragranyl acetate and fragranol were detected in remarkable concentrations in sample 8. The fruits of sample 8 were then cultivated under controlled agronomic conditions, providing plants rich in these compounds (sample 9). The geographical variability influenced the EO compositio...
Arabian flora is a rich source of bioactive compounds. In this study, we investigated three aroma... more Arabian flora is a rich source of bioactive compounds. In this study, we investigated three aromatic plant species with the aim of finding valuable sources of antimicrobial agents against common pathogenic microorganisms. We focused especially on microorganisms, which cause outbreaks of infectious disease during mass gatherings and pilgrimages season in Saudi Arabia. The essential oils of three aromatic plant species were hydrodistilled from flowering aerial parts of Lavandula pubescens Decne. and Pulicaria incisa subsp. candolleana E.Gamal-Eldin, and from leaves, stems, ripe and unripe fruits of Juniperus procera Hochst. Ex Endl. They were subsequently analyzed by gas chromatography-mass spectrometry (GC-MS). The main constituents of L. pubescens were found to be carvacrol (55.7%), methyl carvacrol (13.4%), and β-bisabolene (9.1%). P. incisa subsp. Candolleana essential oil was rich in linalool (33.0%), chrysanthenone (10.3%), eugenol (8.9%), and cis-chrysanthenol (8.0%); the major...
Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russeliosid... more Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n=8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-α and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as famotidine.
In developing countries, crop deterioration is mainly caused by inappropriate storage conditions ... more In developing countries, crop deterioration is mainly caused by inappropriate storage conditions that promote insect infestation. Synthetic pesticides are associated with serious adverse effects on humans and the environment. Thus, finding alternative “green” insecticides is a very pressing need. Calotropis procera (Aiton) Dryand (Apocynaceae) growing in Saudi Arabia was selected for this purpose. LC-MS/MS analysis was applied to investigate the metabolic composition of different C. procera extracts. Particularly, C. procera latex and leaves showed a high presence of cardenolides including calactin, uscharidin, 15β-hydroxy-calactin, 16β-hydroxy-calactin, and 12β-hydroxy-calactin. The ovicidal activity of the extracts from different plant organs (flowers, leaves, branches, roots), and of the latex, against Cadra cautella (Walker) (Lepidoptera, Pyralidae) was assessed. Extracts of C. procera roots displayed the most potent activity with 50% of C. cautella eggs not hatching at 10.000 p...
Phytochemical study of the ethanolic extract of the fruits of Gleditsia aquatica and Gleditsia ca... more Phytochemical study of the ethanolic extract of the fruits of Gleditsia aquatica and Gleditsia caspica resulted in the isolation of the triterpene saponins; aquaticasaponin A (1), aquaticasaponin B (2), caspicaoside L (3) and caspicaoside M (4). Compound (1) showed good activity against methicillin resistant Staphylococcus aureus (MRSA) (IC50 =16.3 μg/mL) and Staphylococcus aureus (non-MRSA), (IC50 =12.2 μg/mL) and it expressed considerable cytotoxic activity against BT-549 (Human Ductal Carcinoma, Breast), KB (Human Epidermal Carcinoma, Oral) and SK-MEL (Human Malignant Melanoma) with IC50 values of 8.3, 10.0 and 3.3 μg/mL, respectively. Compounds (2) and (3) showed potent cytotoxicity against BT-549 with IC50 values of 5.3 and 7.3 μg/mL, and against SK-MEL with IC50 values of 4.3 and 3.1 μg/mL, respectively. Compound (4) showed good cytotoxicity against KB with IC50 value of 7.3 μg/mL. In consistent, the study of molecular determinates of cytotoxic activity of these new scaffolds ...
Evidence-Based Complementary and Alternative Medicine, 2021
4-O-Podophyllotoxin sulfamate derivatives were prepared using the natural lignan podophyllotoxin.... more 4-O-Podophyllotoxin sulfamate derivatives were prepared using the natural lignan podophyllotoxin. The prepared compounds were afforded by reacting O-sulfonyl chloride podophyllotoxin with ammonia or aminoaryl/heteroaryl motif. Biological evaluation was performed in human breast cancer (MCF7), ovarian cancer (A2780), colon adenocarcinoma (HT29), and normal lung fibroblast (MRC5) cell lines. Compound 3 exhibited potent inhibitory activity and good selectivity margin. Compounds 2, 3, and 7 exerted apoptotic effect in MCF7 cells in a dose-dependent manner. The cytotoxicity of the verified compounds was inferior to that of podophyllotoxin.
We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells a... more We evaluate how 3-acetylation modulates the in vitro activity of ursolic acid in melanoma cells alone or in combination treatments with quercetin. Anti-proliferative studies on A375 cells and adult human dermal fibroblasts included analyses on cell cycle distribution, caspase activity, phosphatidylserine translocation, cell morphology and Bax/Bcl-2 protein expression. Then, 2D and 3D migration of B16F10 cells were studied using scratch and Transwell assays, respectively. Ursolic acid and 3-O-acetylursolic acid have shown similar GI50 on A375 cells (26 µM vs. 32 µM, respectively) significantly increased both early and late apoptotic populations, activated caspases 3/7 (48–72 h), and enhanced Bax whilst attenuating Bcl-2 expression. Ursolic acid caused elevation of the sub-G1 population whilst its 3-acetyl derivative arrested cell cycle at S phase and induced strong morphological changes. Combination treatments showed that ursolic acid and quercetin act synergistically in migration as...
Acute myeloid leukemia (AML) is among the top four malignancies in Saudi nationals, and it is the... more Acute myeloid leukemia (AML) is among the top four malignancies in Saudi nationals, and it is the top leukemia subtype worldwide. Resistance to available AML drugs requires the identification of new targets and agents. Hsp90 is one of the emerging important targets in AML, which has a central role in the regulation of apoptosis and cell proliferation through client proteins including the growth factor receptors and cyclin dependent kinases. The objective of the first part of this study is to investigate the putative Hsp90 inhibition activity of three novel previously synthesized quinazolines, which showed HL60 cytotoxicity and VEGFR2 and EGFR kinases inhibition activities. Using surface plasmon resonance, compound 1 (HAA2020) showed better Hsp90 inhibition compared to 17-AAG, and a docking study revealed that it fits nicely into the ATPase site. The objective of the second part is to maximize the anti-leukemic activity of HAA2020, which was combined with each of the eleven standard ...
In this paper, the isolation of one new iridoid glucoside, 6β-acetoxyipolamiide (1), and thirteen... more In this paper, the isolation of one new iridoid glucoside, 6β-acetoxyipolamiide (1), and thirteen (2 – 14) known congeners from two Lamiaceae species, Stachys ocymastrum and Premna resinosa, leaf extracts is reported. The structural determination of the isolated compounds was performed by mono- and bidimensional NMR spectroscopic analysis as well as MS experiments. The isolates were assayed for their antiangiogenic activity by two in vivo models, zebrafish embryos and chick chorioallantoic membrane assays. The compounds with a significant antiangiogenic activity in both assays were β-hydroxyipolamiide (2), ipolamiide (3), and buddlejoside A5 (8). 6-O-α-l-(3″-O-p-Methoxycinnamoyl-4″-O-acetyl)rhamnopyranosyl catalpol (13) and 6-O-α-l-(2″-trans-caffeoyl)rhamnopyranosyl catalpol (6) showed the best antiangiogenic response on blood vessel growth in zebrafish embryos, whereas saccatoside (10) and 6-O-α-l-(2″-O - p-methoxycinnamoyl-3″-O-acetyl)rhamnopyranosyl catalpol (14) resulted in a st...
Angiogenesis plays a crucial role in malignant tumor progression and development. The present stu... more Angiogenesis plays a crucial role in malignant tumor progression and development. The present study aimed to identify lead plants with selective anti-angiogenic properties. A total of 26 methanolic extracts obtained from 18 plants growing in Saudi Arabia and Jordan that belong to the Lamiaceae family were screened for their cytotoxic and anti-angiogenic activities using MTT and rat aortic ring assays, respectively. Four novel extracts of Thymbra capitata (L.) Cav., Phlomis viscosa Poir, Salvia samuelssonii Rech.f., and Premna resinosa (Hochst.) Schauer were identified for their selective anti-angiogenic effects. These extracts did not exhibit cytotoxic effects on human endothelial cells (EA.hy926) indicating the involvement of indirect anti-angiogenic mechanisms. The active extracts are potential candidates for further phytochemical and mechanistic studies.
The surface extract of an accession of Psiadia punctulata (DC.) Vatke (Asteraceae) growing in Sau... more The surface extract of an accession of Psiadia punctulata (DC.) Vatke (Asteraceae) growing in Saudi Arabia was investigated for its phytochemical composition. A bio-guided investigation of the extract led to the isolation of thirteen ent-kaurane and trachylobane diterpenes and seventeen compounds previously described, including nine flavonoids and eight diterpenes. Three flavonoids and one ent-kaurane diterpene showed antimicrobial activity with MIC100 values ranging from 25 to 150 μg/ml. The extract showed antibacterial activity against Staphylococcus aureus (MIC = 180 μg/ml) and antifungal activity against Candida albicans (MIC = 130 μg/ml). The isolated 3',4',5,7-tetramethoxyflavone, at a concentration of 40 μg/ml, displayed the ability to reduce biofilm formation of S. aureus and C. albicans by 50% and 90% respectively.
Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were i... more Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, 1H-13C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showe...
The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydroch... more The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics o...
Uploads
Papers by Ammar Bader