title: Synthesis of imidazole-containing analogues of farnesyl pyrophosphate and evaluation of their biological activity on protein farnesyltransferase.
abstract: With the aim of creating new bisubstrate inhibitors of protein farnesyltransferase (FTase), new carboxylic farnesyl pyrophosphate analogues have been designed and synthesized. The original structures are built around three elements: a prenyl moiety, a 1,4-diacid motif and an imidazole ring. All the compounds were evaluated for their ability to inhibit FTase and compared with the corresponding derivatives lacking the imidazole ring, synthesized for that purpose. These new compounds are not bisubstrate inhibitors probably because the imidazole ring is not in the right position to interact with the zinc atom. However these derivatives display FPP competitive inhibition with a good activity in the carboxylic farnesyl pyrophosphate analogues series.
authors: Institut de Chimie des Substances Naturelles, CNRS, Gif sur Yvette, France.
authors: Laëtitia
authors: L
authors: Coudray
authors: Renata Marcia
authors: RM
authors: de Figueiredo
authors: Stéphanie
authors: S
authors: Duez
authors: Sylvie
authors: S
authors: Cortial
authors: Joëlle
authors: J
authors: Dubois
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011106:Polyisoprenyl Phosphates; D011714:Pyrans; D012717:Sesquiterpenes; D009569:Nitric Oxide; C004808:farnesyl pyrophosphate; D051231:Farnesyltranstransferase