Bioactive withanolides from Withania obtusifolia

Seven withanolides were isolated from the leaves of Withania obtusifolia. Of these, one was new [obtusifonolide (1)], five were new to the species [sitoindoside IX (2), 6 alpha-chloro-5 beta-hydroxy withaferin A (3), isowithanone (4), 2,3-dihydro-3-ethoxywithaferin A (5), and daturataturin A (6)], and one was reported previously from W. obtusifolia [withaferin A (7)]. The structures were elucidated using a set of spectroscopic and spectrometric techniques. Compounds (1-7) were evaluated for cytotoxicity against a human cancer cell panel and for antimicrobial activity in an array of bacteria and fungi. Compound 7 showed cytotoxic activity against the MDA-MB-435 (human melanoma) and SW-620 (human colon cancer) cell lines with IC50 values of 1.7 and 0.3 mu M, respectively. The in vitro activity of 7 on 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase was also investigated. (C) 2014 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.