Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors

N Beaurain; C Mésangeau; P Chavatte; G Ferry; V Audinot; J A Boutin; P Delagrange; C Bennejean; S Yous

doi:10.1080/1475636021000005721

Design, synthesis and in vitro evaluation of novel derivatives as serotonin N-acetyltransferase inhibitors

J Enzyme Inhib Med Chem. 2002 Dec;17(6):409-14. doi: 10.1080/1475636021000005721.

Authors

N Beaurain¹, C Mésangeau, P Chavatte, G Ferry, V Audinot, J A Boutin, P Delagrange, C Bennejean, S Yous

Affiliation

¹ Laboratoire de Chimie Thérapeutique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, BP 83, 59006 Lille Cédex, France.

PMID: 12683677
DOI: 10.1080/1475636021000005721

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).

MeSH terms

Arylamine N-Acetyltransferase / antagonists & inhibitors*
Databases, Factual
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Inhibitory Concentration 50
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Arylamine N-Acetyltransferase