Synthesis and Biological Evaluation of Kibdelone C and Its Simplified Derivatives.
J Am Chem Soc
; 138(33): 10561-70, 2016 08 24.
Article
em En
| MEDLINE
| ID: mdl-27459345
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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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Xantonas
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article