期刊
PURE AND APPLIED CHEMISTRY
卷 84, 期 6, 页码 1353-1367出版社
WALTER DE GRUYTER GMBH
DOI: 10.1351/PAC-CON-11-10-08
关键词
antiproliferative; Physalis longifolia; Solanaceae; structure classification; structure-activity relationship; Vassobia breviflora; Withania somnifera; withanolide
资金
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR015563] Funding Source: NIH RePORTER
- Biotechnology and Biological Sciences Research Council [BB/C503662/1] Funding Source: Medline
- NCRR NIH HHS [P20 RR015563] Funding Source: Medline
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 mu M, 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 Delta(2)-1-oxo-functionality in ring A, a 5 beta,6 beta-epoxy or 5 alpha-chloro-6 beta-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.
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