Synthesis and biological evaluation of a new series of N-ylides as protein farnesyltransferase inhibitors

Cristina-Maria Abuhaie; Alina Ghinet; Amaury Farce; Joëlle Dubois; Benoît Rigo; Elena Bîcu

doi:10.1016/j.bmcl.2013.08.088

Synthesis and biological evaluation of a new series of N-ylides as protein farnesyltransferase inhibitors

Bioorg Med Chem Lett. 2013 Nov 1;23(21):5887-92. doi: 10.1016/j.bmcl.2013.08.088. Epub 2013 Sep 3.

Authors

Cristina-Maria Abuhaie¹, Alina Ghinet, Amaury Farce, Joëlle Dubois, Benoît Rigo, Elena Bîcu

Affiliation

¹ Department of Organic Chemistry, 'Al. I. Cuza' University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania.

PMID: 24054122
DOI: 10.1016/j.bmcl.2013.08.088

Abstract

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.

Keywords: Anticancer agent; Farnesyltransferase inhibitor; N-Ylide; Phenothiazine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase / antagonists & inhibitors*
Farnesyltranstransferase / metabolism
Humans
Molecular Docking Simulation
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Farnesyltranstransferase