Anti-proliferative withanolides from the Solanaceae: a structure-activity study
View/ Open
Issue Date
2012-04-01Author
Zhang, Huaping
Samadi, Abbas K.
Cohen, Mark S.
Timmermann, Barbara N.
Publisher
De Gruyter
Type
Article
Article Version
Scholarly/refereed, publisher version
Metadata
Show full item recordAbstract
As part of our search for bioactive compounds from plant biodiversity, 29 withanolides were recently isolated from three members of the Solanaceae: Physalis longifolia, Vassobia breviflora, and Withania somnifera. Six derivatives were prepared from these naturally occurring withanolides. All compounds were evaluated for in vitro antiproliferative activity against an array of cell lines [melanoma cell lines (B16F10, SKMEL28); human head and neck squamous cell carcinomas (HNSCC) cell lines (JMAR, MDA1986, DR081-1); breast cancer cell line (Hs578T), and non-malignant human cell line (MRC5)]. This led to the discovery of 15 withanolides, with IC50 values in the range of 0.067−17.4 μM, including withaferin A, withaferin A 4,27-diacetate, 27-O-glucopyranosylwithaferin A, withalongolide H, withalongolide C, withalongolide A, withalongolide A 4,27-diacetate, withalongolide A 4,19,27-triacetate, withalongolide B, withalongolide B 4-acetate, withalongolide B 4,19-diacetate, withalongolide D, withalongolide E, withalongolide G, and 2,3-dihydrowithaferin A 3-O-sulfate. In order to update the growing literature on withanolides and their activities, we summarized the distribution, structural types, and antiproliferative activities for all published withanolides to date. The structure–activity relationship analysis (SARA) confirmed the importance of the presence of a ∆2-1-oxo-functionality in ring A, a 5β,6β-epoxy or 5α-chloro-6β-hydroxy grouping in ring B, and nine-carbon side chain with a lactone moiety for cytotoxic activity. Conversely, the SARA indicated that the –OH or –OR groups at C-4, 7, 11, 12, 14, 15, 16, 17, 18, 19, 20, 23, 24, 27, and 28 were not contributors to the observed antiproliferative activity within the systems analyzed.
Description
This is the publisher's version, also available electronically from "http://www.degruyter.com".
Collections
- Pharmacy Scholarly Works [293]
Citation
Zhang, H., Samadi, A., Cohen, M. & Timmermann, B. N. (2012) Anti-proliferative withanolides from the Solanaceae: a structure-activity study. Pure and Applied Chemistry, 84(6), 1353-1367. http://www.dx.doi.org/10.1351/pac-con-11-10-08
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.