title: Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase: Synthesis and biological evaluation of new farnesylpyrophosphate analogues.
abstract: Protein farnesyltransferase (FTase) has recently appeared as a new target of parasitic diseases, a field poor in drugs in development. With the aim of creating new bisubstrate inhibitors of FTase, new farnesyl pyrophosphate analogues have been studied. Farnesyl analogues with a malonic acid function exhibited the best inhibitory activity on FTase. This group was introduced into our imidazole-containing model leading to new compounds with submicromolar activities. Kinetic experiments have been realized to determine their binding mode to the enzyme.
authors.affiliation: Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif-sur-Yvette, Avenue de la Terrasse 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Duez
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Coudray
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mouray
authors.forename: Philippe
authors.initials: P
authors.lastname: Grellier
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D011106:Polyisoprenyl Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000254:growth & development
chemical_list: D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D051231:Farnesyltranstransferase