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Synthesis and structure-activity relationships of new benzodioxinic lactones as potential anticancer drugs

M. Romero, P. Renard, D.-H. Caignard, G. Atassi, X. Solans, P. Constans, C. Bailly, and M. D. Pujol. Synthesis and structure-activity relationships of new benzodioxinic lactones as potential anticancer drugs. Journal of Medicinal Chemistry, 50, 294-307 (2007).

Abstract
A set of disubstituted tetracyclic lactones has been synthesized and tested for potential antitumor activity. Several of them possess a noticeable cytotoxicity against L1210 and HT-29 colon cells in vitro. Relationships between chain nature and biological properties were sought. Lactones with a pentyl or hexyl substituent at C-11 are the most active ones. The introduction of a functional group at the side chain of C-11 modified the potency; carboxylic acid and primary amine decreased the cytotoxicity, whereas a cyano group increased the activity. An extensive structure-activity relationship (SAR) study of these derivatives, including carbon homologues and bioisosteres has been performed. The synthesis and cytotoxicity of these compounds are discussed. Two lactones are recognized as potential lead compounds.

Keywords
Ellipticine, benzodioxinic lactones.

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 Synthesis and structure-activity of benzodioxinic lactones