title: Peptide chemistry applied to a new family of phenothiazine-containing inhibitors of human farnesyltransferase.
abstract: Novel phenothiazine derivatives bearing an amino acid residue were synthesized via peptide chemistry, and evaluated for their inhibitory potential on human farnesyltransferase. The phenothiazine unit proved to be an important bulky unit in the structure of the synthesized inhibitors. Propargyl ester 20 bearing a tyrosine residue exhibited the best biological potential in vitro in the present study. Further syntheses and biological evaluation of phenothiazine derivatives are necessary in order to gain a full view of SAR in this family of farnesyltransferase inhibitors.
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; Univ Lille Nord de France, F-59000 Lille, France; UCLille, EA GRIIOT (4481), Laboratoire de pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille, France.
authors.forename: Alina
authors.initials: A
authors.lastname: Ghinet
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: Univ Lille Nord de France, F-59000 Lille, France; UCLille, EA GRIIOT (4481), Laboratoire de pharmacochimie, HEI, 13 rue de Toul, F-59046 Lille, 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: Univ Lille Nord de France, F-59000 Lille, France; Institut de Chimie Pharmaceutique Albert Lespagnol, EA GRIIOT (4481), IFR114, 3 Rue du Pr Laguesse, B.P. 83, F-59006 Lille, 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. Electronic address: dalila@uaic.ro.
authors.forename: Dalila
authors.initials: D
authors.lastname: Belei
mesh_terms: D004305:Dose-Response Relationship, Drug; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D010640:Phenothiazines; D051231:Farnesyltranstransferase; C031637:phenothiazine
keywords: Activated ester; Farnesyltransferase inhibitor; Peptide coupling; Phenothiazine