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.

Keywords: Activated ester; Farnesyltransferase inhibitor; Peptide coupling; Phenothiazine.