Synthesis and biological evaluation of a new series of N-ylides as protein farnesyltransferase inhibitors.
A new family of 30 benzoylated N-ylides 4 and 5 was synthesized and evaluated for the inhibitory activity on human protein farnesyltransferase. Most of these novel compounds possessed in vitro inhibition potencies in the micromolar range. The nature of the substituents on the pyridine and phenyl units proved to be important in determining inhibitory activity and generally, the replacement of the cyanoacrylonitrile function by a cyanoethylacrylate group decreased the biological potential on farnesyltransferase. These results completed our SAR study on this original class of N-ylides.
Department of Organic Chemistry, 'Al. I. Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.
Cristina-Maria
CM
Abuhaie
Alina
A
Ghinet
Amaury
A
Farce
Joëlle
J
Dubois
Benoît
B
Rigo
Elena
E
Bîcu
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase
Anticancer agent; Farnesyltransferase inhibitor; N-Ylide; Phenothiazine