Potent Farnesyltransferase Inhibitors with 1,4-Diazepane Scaffolds as Novel Destabilizing Microtubule Agents in Hormone-Resistant Prostate Cancer.

Nicolas Wlodarczyk , Delphine Le Broc-Ryckewaert , Pauline Gilleron , Amélie Lemoine , Amaury Farce , Philippe Chavatte , Joëlle Dubois (1) , Nicole Pommery , Jean-Pierre Hénichart , Christophe Furman , Régis Millet

1 ICSN - Institut de Chimie des Substances Naturelles

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.

Domaines: Chimie organique

Nicolas Wlodarczyk, Delphine Le Broc-Ryckewaert, Pauline Gilleron, Amélie Lemoine, Amaury Farce, et al.. Potent Farnesyltransferase Inhibitors with 1,4-Diazepane Scaffolds as Novel Destabilizing Microtubule Agents in Hormone-Resistant Prostate Cancer.. Journal of Medicinal Chemistry, 2011, 54 (5), pp.1178-1190. ⟨10.1021/jm101067y⟩. ⟨hal-00581321⟩