title: Investigations on the 2-thiazolylhydrazyne scaffold: synthesis and molecular modeling of selective human monoamine oxidase inhibitors.
abstract: A new series of [4-(3-methoxyphenyl)-thiazol-2-yl]hydrazyne derivatives were synthesized in good yield (71-99%) and characterized by elemental analysis and (1)H NMR studies. The compounds were assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity and most of them showed IC(50) values in the nanomolar range, thus demonstrating our interest in this privileged scaffold. The most active and selective derivative (20), bearing a pyridine moiety on the CN, displayed IC(50)=3.81+/-0.12 nM and selectivity ratio=119 toward hMAO-B. Molecular modeling studies were carried out on recent and high resolution hMAO-A and hMAO-B crystallographic structures to better justify the enzyme-inhibitor interaction toward hMAO isoforms and to explain the structure-activity relationship of this kind of inhibitors.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma La Sapienza, Ple A Moro 5, 00185 Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Chimenti
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Paola
authors.initials: P
authors.lastname: Chimenti
authors.forename: Arianna
authors.initials: A
authors.lastname: Granese
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
authors.forename: Francisco
authors.initials: F
authors.lastname: Orallo
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
mesh_terms: D006801:Humans; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D006861:Hydrogen Peroxide; D008995:Monoamine Oxidase