Synthesis and biological evaluation of epothilone A dimeric compounds.
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.
Passarella
Daniele
D
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, Italy. Daniele.Passarella@unimi.it
Comi
Daniela
D
Cappelletti
Graziella
G
Cartelli
Daniele
D
Gertsch
Juerg
J
Quesada
Ana R
AR
Borlak
Jurgen
J
Altmann
Karl-Heinz
KH
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D019281:Dimerization; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000166:cytology; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D020533:Angiogenesis Inhibitors; D034261:Epothilones; D014404:Tubulin; D050257:Tubulin Modulators; C093787:epothilone A