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Withaferin a-Related Steroids From Withania Aristata Exhibit Potent Antiproliferative Activity by Inducing Apoptosis in Human Tumor Cells
Posted by Admin, Senior Editor in Ashwagandha
Authored by PubMed
Topics: Ashwagandha Withania Somnifera

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Llanos GG, Araujo LM, Jim?nez IA, Moujir LM, Bazzocchi IL. Withaferin A-related steroids from Withania aristata exhibit potent antiproliferative activity by inducing apoptosis in human tumor cells. 1. Eur J Med Chem. 2012 Aug;54:499-511. Epub 2012 Jun 1.
Six new withanolides (1-6) along with eleven known ones (7-17) were isolated from the leaves of Withania aristata. Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques. Semisynthesis of the minority metabolites 7 and 15 from compounds 6 and 9, respectively, as starting material, was performed. The isolated compounds as well as three derivatives (7a, 9a and 9b) of withaferin A were evaluated for cytotoxicity against HeLa (carcinoma of the cervix), A-549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) human cancer cell lines, and against normal Vero cells (African green monkey kidney). Five compounds from this series (8, 9a, 9b, 11 and 13) exhibited potent antiproliferative effects on the tumor cells, even higher than the well known anticancer agent, withaferin A (9). Phosphatidylserine externalization, chromatin condensation, and caspase-3 activation clearly indicated apoptosis as a mechanism of action. The structure-activity relationship revealed valuable information on the pharmacophore for withanolide-type compounds.

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