Synthesis and biological evaluation of a new series of phenothiazine-containing protein farnesyltransferase inhibitors

Cristina-Maria Abuhaie; Alina Ghinet; Amaury Farce; Joëlle Dubois; Philippe Gautret; Benoît Rigo; Dalila Belei; Elena Bîcu

doi:10.1016/j.ejmech.2012.11.008

Synthesis and biological evaluation of a new series of phenothiazine-containing protein farnesyltransferase inhibitors

Eur J Med Chem. 2013 Jan:59:101-10. doi: 10.1016/j.ejmech.2012.11.008. Epub 2012 Nov 14.

Authors

Cristina-Maria Abuhaie¹, Alina Ghinet, Amaury Farce, Joëlle Dubois, Philippe Gautret, Benoît Rigo, Dalila Belei, 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: 23207411
DOI: 10.1016/j.ejmech.2012.11.008

Abstract

Two new families of human farnesyltransferase inhibitors 13a-m and 14a-d, based on a phenothiazine scaffold, were synthesized. Compounds 14a and 14b were the most promising inhibitors of human farnesyltransferase with IC(50) values of 0.7 and 0.6 μM, respectively.

Publication types

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

MeSH terms

Catalytic Domain
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Farnesyltranstransferase / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Models, Molecular
Molecular Structure
Phenothiazines / chemistry
Phenothiazines / pharmacology

Substances

Enzyme Inhibitors
Phenothiazines
Farnesyltranstransferase