title: Potent farnesyltransferase inhibitors with 1,4-diazepane scaffolds as novel destabilizing microtubule agents in hormone-resistant prostate cancer.
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.
authors.affiliation: Institut de Chimie Pharmaceutique Albert Lespagnol, Université Lille-Nord de France, EA4481, IFR114, 3 Rue du Pr Laguesse, BP 83, F-59006 Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wlodarczyk
authors.forename: Delphine
authors.initials: D
authors.lastname: Le Broc-Ryckewaert
authors.forename: Pauline
authors.initials: P
authors.lastname: Gilleron
authors.forename: Amélie
authors.initials: A
authors.lastname: Lemoine
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Nicole
authors.initials: N
authors.lastname: Pommery
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hénichart
authors.forename: Christophe
authors.initials: C
authors.lastname: Furman
authors.forename: Régis
authors.initials: R
authors.lastname: Millet
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D001381:Azepines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008958:Models, Molecular; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects / Q000648:ultrastructure; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C545228:1,4-diazepane; D000726:Androgen Antagonists; D001381:Azepines; D014404:Tubulin; D050257:Tubulin Modulators; D051231:Farnesyltranstransferase