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).
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
Ellipticine, benzodioxinic lactones.
Synthesis and structure-activity of benzodioxinic lactones