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Anti-proliferative withanolides from the Solanaceae: a structure-activity study.
Huaping Zhang1, Abbas K Samadi, Mark S Cohen
1Department of Medicinal Chemistry, School of Pharmacy, University of Kansas, Lawrence, KS 66045, United States.
Pure and Applied Chemistry. Chimie Pure Et Appliquee
|October 8, 2013
Summary
This study isolated 29 withanolides from Solanaceae plants and synthesized 6 derivatives, discovering 15 compounds with anti-proliferative activity against cancer cell lines. Structure-activity relationship analysis identified key structural features for cytotoxic effects.
Area of Science:
- Natural Product Chemistry
- Medicinal Chemistry
- Pharmacology
Background:
- Withanolides are a class of naturally occurring steroidal lactones found in plants of the Solanaceae family.
- These compounds have demonstrated a wide range of biological activities, including anti-inflammatory, immunomodulatory, and anti-cancer properties.
- Ongoing research aims to discover novel withanolides and elucidate their therapeutic potential.
Purpose of the Study:
- To isolate and characterize withanolides from *Physalis longifolia*, *Vassobia breviflora*, and *Withania somnifera*.
- To evaluate the in vitro anti-proliferative activity of isolated and synthesized withanolides against various cancer cell lines.
- To update the literature on withanolide distribution, structural diversity, and anti-proliferative activities, and to perform a structure-activity relationship analysis.
Main Methods:
- Isolation of 29 withanolides from three Solanaceae plant species using chromatographic techniques.
- Synthesis of six derivatives from naturally occurring withanolides.
- In vitro anti-proliferative assays against melanoma, head and neck squamous cell carcinoma, and breast cancer cell lines.
- Structure-activity relationship (SARA) analysis of all published withanolides.
Main Results:
- Fifteen withanolides exhibited significant in vitro anti-proliferative activity, with IC50 values ranging from 0.067 to 17.4 µM.
- Specific compounds like withaferin A and several withalongolides demonstrated potent cytotoxic effects.
- SARA analysis identified critical structural features, including specific functionalities in rings A and B and the side chain, essential for cytotoxic activity.
Conclusions:
- The study successfully identified and characterized multiple withanolides with promising anti-proliferative potential against cancer cells.
- The findings contribute to the understanding of withanolide structure-activity relationships, guiding the development of novel anti-cancer agents.
- This research underscores the importance of Solanaceae plants as a source of bioactive compounds for drug discovery.
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