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...
In a project to investigate the chemistry of South African Plectranthus species, from the dichlor... more In a project to investigate the chemistry of South African Plectranthus species, from the dichloromethane extract of the aerial parts of Plectranthus venteri, we isolated two known natural product acetophenones, namely 2-hydroxy-3,4,5,6-tetramethoxy-acetophenone (1) and 2-hydroxy-4,5,6-trimethoxy-acetophenone (2). Structures were assigned using NMR spectroscopy and HRTOFESIMS. Compound 1 was previously synthesised as a precursor to the polymethoxylated flavone nobiletin. The acetophenones exhibited remarkable inhibitory activities against the transfer of the IncW plasmid R7K in a bacterial plasmid transfer inhibition assay.
Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to... more Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These ...
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...
In a project to investigate the chemistry of South African Plectranthus species, from the dichlor... more In a project to investigate the chemistry of South African Plectranthus species, from the dichloromethane extract of the aerial parts of Plectranthus venteri, we isolated two known natural product acetophenones, namely 2-hydroxy-3,4,5,6-tetramethoxy-acetophenone (1) and 2-hydroxy-4,5,6-trimethoxy-acetophenone (2). Structures were assigned using NMR spectroscopy and HRTOFESIMS. Compound 1 was previously synthesised as a precursor to the polymethoxylated flavone nobiletin. The acetophenones exhibited remarkable inhibitory activities against the transfer of the IncW plasmid R7K in a bacterial plasmid transfer inhibition assay.
Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to... more Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1). These compounds also displayed moderate inhibitory effects on Klebsiella and Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and cytotoxicity assays were used to evaluate these compounds. Of particular note was their ability to inhibit mycobacterial drug efflux and biofilm formation, while maintaining a high selectivity towards M. tuberculosis H37Rv. These ...
Uploads
Papers by Proma Khondkar