title: Synthesis, molecular modeling, and in vitro screening of monoamine oxidase inhibitory activities of some novel hydrazone derivatives.
abstract: Thirteen 2-[2-(5-methyl-2-benzoxazolinone-3-yl)acetyl]-3/4/5-substituted benzylidenehydrazine derivatives were synthesized by reacting 2-(5-methyl-2-benzoxazolinone-3-yl)acetylhydrazine and substituted benzaldehydes in neutral and acid/base catalyzed conditions, and a comparison was made in terms of their yields and reaction times. The structures of all compounds were confirmed by IR, (1)H NMR, (13)C NMR, mass spectral data, and elemental analyses. All the compounds were investigated for their ability to selectively inhibit MAO isoforms by in vitro tests and were found to inhibit recombinant human MAO-B selectively and reversibly in a competitive manner. Among the compounds examined, compound 16 was found to be more selective than selegiline, a known MAO-B inhibitor, in respect to the K i values experimentally found. Additionally, compounds 9 and 15 showed moderate MAO-B inhibitor activity. The interaction of compounds with MAO isoforms was investigated by molecular docking studies using recently published crystallographic models of MAO-A and MAO-B. The results obtained from the docking studies were found to be in good agreement with the experimental values.
authors: Department of Pharmaceutical Chemistry, Hacettepe University, Sıhhıye, 06100, Ankara, Turkey.
authors: Umut
authors: U
authors: Salgin-Gökşen
authors: Nesrin
authors: N
authors: Gökhan-Kelekçi
authors: Samiye
authors: S
authors: Yabanoglu-Çiftci
authors: Kemal
authors: K
authors: Yelekçi
authors: Gülberk
authors: G
authors: Uçar
mesh_terms: D004353:Drug Evaluation, Preclinical; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D066298:In Vitro Techniques; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D006835:Hydrazones; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase