title: Synthesis and biological evaluation of potential bisubstrate inhibitors of protein farnesyltransferase. Design and synthesis of functionalized imidazoles.
abstract: A novel series of compounds, derived from 2,5-functionalized imidazoles, have been synthesized as potential bisubstrate inhibitors of protein farnesyltransferase (FTase) using structure-based design. These compounds have a 1,4-diacid chain and a tripeptide connected by an imidazole ring. The synthetic strategy relies on the functionalization at the C-2 position of the heterocycle with the diacid side chain and peptide coupling at the C-5 position. Several new compounds were synthesized in good yields. Kinetic experiments on the most active compounds revealed different binding modes depending on the diacid chain length.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette cedex, France.
authors.forename: Renata Marcia
authors.initials: RM
authors.lastname: de Figueiredo
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Coudray
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase