New indolizine-chalcones as potent inhibitors of human farnesyltransferase: Design, synthesis and biological evaluation.
A new family of indolizine-chalcones was designed, synthesized and screened for the inhibitory potential on human farnesyltransferase in vitro to identify potent antitumor agents. The most active compound was phenothiazine 2a, exhibiting an IC50 value in the low nanomolar range, similar to that of known FTI-276, highly potent farnesyltransferase inhibitor. The newly synthesized indolizine-chalcones 2a-d constitute the most efficient inhibitors of farnesyltransferase bearing a phenothiazine unit known to date.
'Alexandru Ioan Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.
Iuliana-Monica
IM
Moise
'Alexandru Ioan Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania; Hautes Etudes d'Ingénieur (HEI), Groupe HEI-ISA-ISEN, UCLille, Laboratoire de Pharmacochimie, 13 rue de Toul, F-59046 Lille, France; Inserm U995, LIRIC, Université de Lille, CHRU de Lille, Faculté de médecine-Pôle recherche, Place Verdun, F-59045 Lille Cedex, France.
Alina
A
Ghinet
'Alexandru Ioan Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.
Dalila
D
Belei
Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif, Avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France.
Joëlle
J
Dubois
Inserm U995, LIRIC, Université de Lille, CHRU de Lille, Faculté de médecine-Pôle recherche, Place Verdun, F-59045 Lille Cedex, France; Faculté des Sciences Pharmaceutiques et Biologiques de Lille, 3 Rue du Pr Laguesse, B.P. 83, F-59006 Lille, France.
Amaury
A
Farce
'Alexandru Ioan Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania. Electronic address: elena@uaic.ro.
Elena
E
Bîcu
D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007212:Indolizines / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D047188:Chalcones; D004791:Enzyme Inhibitors; D007212:Indolizines; C035094:indolizine; D051231:Farnesyltranstransferase
Antitumor agent; Chalcone; Farnesyltransferase inhibitor; Indolizine; Phenothiazine