Abstract
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), 6α-chloro-5β-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 0.3μM, respectively. The in vitro activity of 7 on 17β-hydroxysteroid dehydrogenase and 5α-reductase was also investigated.
Highlights
The withanolides are a group of naturally occurring polyoxygenated C-28 ergostane-type steroids (Chen et al, 2011, Lavie et al, 1965)
Sub-fractions P08-5 and P10-3 were found to be rich in withanolides as evidenced by thin layer chromatography (TLC), and were purified further using preparative and semipreparative reversed-phase high performance liquid chromatography (RP-HPLC) to yield seven compounds (1–7) with >95% purity as evidenced by ultra-performance liquid chromatography (UPLC) (Fig. S1, Supplementary data)
Six known withanolides were identified by 1- and 2-dimensional nuclear magnetic resonance (1and 2D-NMR), high-resolution mass spectrometry (HRMS) analyses, and comparisons to literature data: sitoindoside IX (2) (Ghosal et al, 1988), 6α-chloro-5β-hydroxy withaferin A (3) (Nittala et al, 1981), isowithanone (4) (Lala et al, 2006), 2,3-dihydro-3-ethoxywithaferin A (5) (Pelletier et al, 1979), daturataturin A (6) (Shingu et al, 1990), and withaferin A (7) (Lavie et al, 1965)
Summary
The withanolides are a group of naturally occurring polyoxygenated C-28 ergostane-type steroids (Chen et al, 2011, Lavie et al, 1965). Withanolides occur largely, but not exclusively, in genera belonging to the plant family Solanaceae, including Withania, Lycium, Datura, Dunalia, Acnistus, Jaborosa, Nicandra, and Physalis (Misico et al, 2011). Withaferin A, isolated in 1965, was the first withanolide to be characterized from Withania somnifera (Lavie et al, 1965) and from Acnistus arborescens (Kupchan et al, 1965). It showed in vitro and in vivo cytotoxic activity against an array of tumor cells (Glotter, 1991, Samadi et al, 2010). As part of an ongoing project to explore medicinal plants of Jordan for anticancer leads (Alali et al, 2005, Alali et al, 2008, Alali et al, 2010), seven withanolides (1–7), of which one was new, were isolated and characterized from an ethanolic extract of the leaves of Withania obtusifolia
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