title: Phenothiazine-based CaaX competitive inhibitors of human farnesyltransferase bearing a cysteine, methionine, serine or valine moiety as a new family of antitumoral compounds.
abstract: A new family of CaaX competitive inhibitors of human farnesyltransferase based on phenothiazine and carbazole skeleton bearing a l-cysteine, l-methionine, l-serine or l-valine moiety was designed, synthesized and biologically evaluated. Phenothiazine derivatives proved to be more active than carbazole-based compounds. Phenothiazine 1b with cysteine residue was the most promising inhibitor of human farnesyltransferase in the current study.
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania.
authors.forename: Gina-Mirabela
authors.initials: GM
authors.lastname: Dumitriu
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Bîcu
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania.
authors.forename: Dalila
authors.initials: D
authors.lastname: Belei
authors.affiliation: Inserm, LIRIC-U995, Université de Lille 2, CHRU de Lille, Faculté de Médecine-Pôle Recherche, Place Verdun, F-59045 Lille Cedex, France; Hautes Etudes d'Ingénieur (HEI), UCLille, Laboratoire de pharmacochimie, 13 rue de Toul, BP 41290, F-59014 Lille Cedex, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Rigo
authors.affiliation: Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif, Avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.affiliation: Inserm, LIRIC-U995, Université de Lille 2, CHRU de Lille, Faculté de Médecine-Pôle Recherche, Place Verdun, F-59045 Lille Cedex, France; Université de Lille 2, Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Chimie Thérapeutique, 3 rue du Professeur Laguesse, BP 83, F-59006 Lille Cedex, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, 'Al. I. Cuza' University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506 Iasi, Romania; Inserm, LIRIC-U995, Université de Lille 2, CHRU de Lille, Faculté de Médecine-Pôle Recherche, Place Verdun, F-59045 Lille Cedex, France; Hautes Etudes d'Ingénieur (HEI), UCLille, Laboratoire de pharmacochimie, 13 rue de Toul, BP 41290, F-59014 Lille Cedex, France. Electronic address: alina.ghinet@hei.fr.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014633:Valine / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010640:Phenothiazines; D012694:Serine; D008715:Methionine; D051231:Farnesyltranstransferase; C031637:phenothiazine; D014633:Valine; D003545:Cysteine
keywords: CAAX inhibitor; Cysteine; Farnesyltransferase; Methionine; Phenothiazine; Serine; Valine