Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives

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• 作者：Janjira Rujirawanich ; Soyeon Kim ; Ai-Jun Ma ; John R. Butler ; Yizhong Wang ; Chao Wang ; Michael Rosen ; Bruce Posner ; Deepak Nijhawanc ; Joseph M. Ready
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：August 24, 2016
• 年：2016
• 卷：138
• 期：33
• 页码：10561-10570
• 全文大小：837K
• 年卷期：0
• ISSN：1520-5126

文摘

Poylcyclic tetrahydroxanthones comprise a large class of cytototoxic natural products. No mechanism of action has been described for any member of the family. We report the synthesis of kibdelone C and several simplified analogs. Both enantiomers of kibdeleone C show low nanomolar cytotoxicity toward multiple human cancer cell lines. Moreover, several simplified derivatives with improved chemical stability display higher activity than the natural product itself. In vitro studies rule out interaction with DNA or inhibition of topoisomerase, both of which are common modes of action for polycyclic aromatic compounds. However, celluar studies reveal that kibdelone C and its simplified derivatives disrupt the actin cytoseketon without directly binding actin or affecting its polymerization in vitro.