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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)10561-10570
Number of pages10
JournalJournal of the American Chemical Society
Volume138
Issue number33
DOIs
StatePublished - Aug 24 2016

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Biological Products
Actins
Polycyclic Compounds
Derivatives
Enantiomers
Aromatic compounds
Chemical stability
Cytotoxicity
Polymerization
DNA
Cells
Cell Line
Neoplasms
kibdelone C
In Vitro Techniques
Inhibition (Psychology)

ASJC Scopus subject areas

  • Catalysis
  • Biochemistry
  • Chemistry(all)
  • Colloid and Surface Chemistry

Cite this

Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives. / Rujirawanich, Janjira; Kim, Soyeon; Ma, Ai Jun; Butler, John R.; Wang, Yizhong; Wang, Chao; Rosen, Michael; Posner, Bruce; Nijhawanc, Deepak; Ready, Joseph M.

In: Journal of the American Chemical Society, Vol. 138, No. 33, 24.08.2016, p. 10561-10570.

Research output: Contribution to journalArticle

Rujirawanich, Janjira ; Kim, Soyeon ; Ma, Ai Jun ; Butler, John R. ; Wang, Yizhong ; Wang, Chao ; Rosen, Michael ; Posner, Bruce ; Nijhawanc, Deepak ; Ready, Joseph M. / Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives. In: Journal of the American Chemical Society. 2016 ; Vol. 138, No. 33. pp. 10561-10570.
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