Potent farnesyltransferase inhibitors with 1, 4-diazepane scaffolds as novel destabilizing microtubule agents in hormone-resistant prostate cancer

N Wlodarczyk, D Le Broc-Ryckewaert…

Index: Wlodarczyk, Nicolas; Le Broc-Ryckewaert, Delphine; Gilleron, Pauline; Lemoine, Amelie; Farce, Amaury; Chavatte, Philippe; Dubois, Joelle; Pommery, Nicole; Henichart, Jean-Pierre; Furman, Christophe; Millet, Regis Journal of Medicinal Chemistry, 2011 , vol. 54, # 5 p. 1178 - 1190

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Citation Number: 13

Abstract

A new class of potent farnesyltransferase inhibitors based on a 1, 4-diazepane scaffold was synthesized with protein farnesyltransferase inhibition potencies in the low nanomolar range. The compounds block the growth on two hormone-resistant tumor prostatic cell lines (DU145 and PC3). The advanced cellular evaluation of the more potent farnesyltransferase inhibitors was explored and revealed a disorganization of tubulin in PC3 cells.