Evaluation of selective human MAO inhibitory activities of some novel pyrazoline derivatives.
A series of 1-[2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetyl]-3,5-diaryl-4,5-dihydro-1H-pyrazole derivatives were prepared by reacting 2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetylhydrazine with appropriate chalcones. The chemical structures of all compounds were confirmed by elemental analyses, IR, (1)H NMR and ESI-MS. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in vitro tests. MAO activities of the compounds were compared with moclobemide and selegiline and all the compounds were found to inhibit human MAO-A selectively. The inhibition profile was found to be competitive and reversible for all compounds by in vitro tests. Among the compounds examined, compounds 5ae, 5af and 5ag were more selective than moclobemide, with respect to the K i values experimentally found. In addition, the compound 5bg showed MAO-A inhibitor activity as well as moclobemide. A series of experimentally tested compounds (5ae-5ch) were docked computationally to the active site of the MAO-A and MAO-B isoenzyme. The AUTODOCK 4.01 program was employed to perform automated molecular docking.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhıye, Ankara, Turkey.
Umut
U
Salgin-Gökşen
Samiye
S
Yabanoğlu-Çiftçi
Ayşe
A
Ercan
Kemal
K
Yelekçi
Gülberk
G
Uçar
Nesrin
N
Gökhan-Kelekçi
D001583:Benzoxazoles / Q000494:pharmacology; D002599:Chalcone / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000187:drug effects; D014316:Tritium
D001583:Benzoxazoles; D008996:Monoamine Oxidase Inhibitors; D014316:Tritium; C017057:benzoxazolone; D002599:Chalcone; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human