Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives

Janjira Rujirawanich; Soyeon Kim; Ai Jun Ma; John R. Butler; Yizhong Wang; Chao Wang; Michael Rosen; Bruce Posner; Deepak Nijhawanc; Joseph M. Ready

doi:10.1021/jacs.6b05484

Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives

Janjira Rujirawanich, Soyeon Kim, Ai Jun Ma, John R. Butler, Yizhong Wang, Chao Wang, Michael Rosen, Bruce Posner, Deepak Nijhawanc, Joseph M. Ready

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20 Scopus citations

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.

Original language	English (US)
Pages (from-to)	10561-10570
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	138
Issue number	33
DOIs	https://doi.org/10.1021/jacs.6b05484
State	Published - Aug 24 2016

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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title = "Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives",

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.",

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AU - Rujirawanich, Janjira

AU - Kim, Soyeon

AU - Ma, Ai Jun

AU - Butler, John R.

AU - Wang, Yizhong

AU - Wang, Chao

AU - Rosen, Michael

AU - Posner, Bruce

AU - Nijhawanc, Deepak

AU - Ready, Joseph M.

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AB - 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.

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Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives

Abstract

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