| Literature DB >> 27459345 |
Janjira Rujirawanich1, Soyeon Kim1, Ai-Jun Ma1, John R Butler1, Yizhong Wang1, Chao Wang1, Michael Rosen1, Bruce Posner1, Deepak Nijhawan1, Joseph M Ready1.
Abstract
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.Entities:
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Year: 2016 PMID： 27459345 PMCID： PMC5004353 DOI： 10.1021/jacs.6b05484
Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419