Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives
Year: 2016
Type: article
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.
DOI: 10.1021/jacs.6b05484
Authors: Janjira Rujirawanich, Soyeon Kim, Ai-Jun Ma, John R. Butler, Yizhong Wang, Chao Wang, Michael Rosen, Bruce Posner, Deepak Nijhawan, Joseph M. Ready
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2505390543