Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors.
Bioorg Med Chem
; 18(14): 5063-70, 2010 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-20579890
ABSTRACT
The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selective inhibitors of hMAO-B isoform in the micromolar or nanomolar range, thus demonstrating that hydrazothiazole could be considered a good pharmacophore to design new hMAO-B inhibitors. Due to the presence in some derivatives of a chiral center, we also performed a semipreparative chromatographic enantioseparation of these compounds obtained by a stereoconservative pattern. The separated enantiomers were submitted to in vitro biological evaluation to point out the stereorecognition of the active site of the enzyme towards these structures. Finally, a 3D-QSAR study was carried out using Comparative Molecular Field Analysis (CoMFA), aiming to deduce rational guidelines for the further structural modification of these lead compounds.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Hidrazonas
/
Monoaminoxidase
/
Inibidores da Monoaminoxidase
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article