title: Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors.
abstract: Serotonin N-acetyltransferase (arylalkylamine N-acetyl-transferase, AANAT) is an enzyme that catalyses the first rate limiting step in the biosynthesis of melatonin (5-methoxy-N-acetyltryptamine). Different physiopathological disorders in human may be due to abnormal secretion of melatonin leading to an inappropriate exposure of melatonin receptors to melatonin. For that reason, we have designed, synthesized and evaluated as inhibitors of human serotonin N-acetyltransferase, a series of compounds that were able to react with coenzyme A to give a bisubstrate analog inhibitor. Compound 12d was found to be a potent AANAT inhibitor (IC50 = 0.18 microM).
authors.affiliation: Laboratoire de Chimie Thérapeutique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, BP 83, 59006 Lille Cédex, France.
authors.forename: N
authors.initials: N
authors.lastname: Beaurain
authors.forename: C
authors.initials: C
authors.lastname: Mésangeau
authors.forename: P
authors.initials: P
authors.lastname: Chavatte
authors.forename: G
authors.initials: G
authors.lastname: Ferry
authors.forename: V
authors.initials: V
authors.lastname: Audinot
authors.forename: J A
authors.initials: JA
authors.lastname: Boutin
authors.forename: P
authors.initials: P
authors.lastname: Delagrange
authors.forename: C
authors.initials: C
authors.lastname: Bennejean
authors.forename: S
authors.initials: S
authors.lastname: Yous
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000037:antagonists & inhibitors*; D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D001191:Arylamine N-Acetyltransferase