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Minor Withanolides of Physalis longifolia: Structure and Cytotoxicity
Zhang, Huaping Motiwala, Hashim F. Samadi, Abbas K. Day, Victor W. Aubé, Jeffrey Cohen, Mark S. Kindscher, Kelly Gollapudi, Rao Timmermann, Barbara N.
Zhang, Huaping
Motiwala, Hashim F.
Samadi, Abbas K.
Day, Victor W.
Aubé, Jeffrey
Cohen, Mark S.
Kindscher, Kelly
Gollapudi, Rao
Timmermann, Barbara N.
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Abstract
In our recent publication on bioactive guided isolation of compounds from Physalis longifolia (Solanaceae) novel anti-proliferative agents withalongolides A (4) and B (5), and their highly cytotoxic analogues, withalongolide A 4,19,27-triacetate (4a) and withalongolide B 4,19-diacetate (5a) were elucidated. In this study, the two lead compounds (4, 5) were re-isolated in gram quantities for the purpose of further analogue preparation and in vivo testing that would continue to probe structure–activity relationships. During this process, two additional withanolides, named withalongolides O (1) and P (2), were elucidated. Their structures were determined by spectroscopic techniques with 1 being subsequently confirmed by X-ray crystallographic analysis. Utilizing a MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] viability assay, withalongolide O (1) and its 4,7-diaceatate (1a), both containing the functionalities of Δ2-1-oxo- in A ring, a 5β,6β-epoxy in B ring, and a lactone ring in the nine-carbon side chain, exhibited potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal lung fibroblast (MRC-5) cells with IC50 values in the range between 0.15 and 2.95 µM. In addition, the previously reported α orientation of 7-acetate group in acnistins C and D should be revised to the β orientation on the basis of NMR data comparison.
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This is the publisher's version, also available electronically from https://www.jstage.jst.go.jp/article/cpb/60/10/60_c12-00305/_article.
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2012-01-01
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Pharmaceutical Society of Japan
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Zhang, Huaping et al. (2012). "Minor Withanolides of Physalis longifolia: Structure and Cytotoxicity." Chemical and Pharmaceutical Bulletin, 60(10):1234-39. http://dx.doi.org/10.1248/cpb.c12-00305.