Synthesis and biological evaluation of epothilone A dimeric compounds

Daniele Passarella, Daniela Comi, Graziella Cappelletti, Daniele Cartelli, Juerg Gertsch, Ana R. Quesada, Jurgen Borlak, Karl-Heinz Altmann, Daniele Passarella, Daniela Comi, Graziella Cappelletti, Daniele Cartelli, Juerg Gertsch, Ana R. Quesada, Jurgen Borlak, Karl-Heinz Altmann

Index: Bioorg. Med. Chem. 17 , 7435-40, (2009)

Full Text: HTML

Abstract

The preparation and biological evaluation of a novel series of dimeric epothilone A derivatives (1-6) are described. Two types of diacyl spacers were introduced to establish the various dimeric epothilone A constructs. The effect of these compounds on tubulin polymerization and their cytotoxicity against four different cancer cell lines are reported. Several of the newly synthesized compounds inhibit endothelial cell differentiation and endothelial cell migration that are key steps of the angiogenic process.