title: Synthesis and Screening of Human Monoamine Oxidase-A Inhibitor Effect of New 2-Pyrazoline and Hydrazone Derivatives.
abstract: A group of 3,5-diaryl-2-pyrazoline and hydrazone derivatives was prepared via the reaction of various chalcones with hydrazide compounds in ethanol. Twenty original compounds were synthesized. Ten of these original compounds have a pyrazoline structure, nine of these original compounds have a hydrazone structure, and one of these original compounds has a chalcone structure. Structural elucidation of the compounds was performed by IR, (1)H NMR, (13)C NMR, mass spectral data, and elemental analyses. These compounds were tested for their inhibitory activities toward the A and B isoforms of human monoamine oxidase (MAO). Except for 3k and 6c, all compounds were found to be competitive, reversible, and selective inhibitors for either one of the isoforms (hMAO-A or MAO-B). Compounds 3k and 6c were found to be competitive, reversible, but non-selective MAO inhibitors. Compound 6h showed hMAO-B inhibitory activity whereas the others potently inhibited hMAO-A. Compound 5c showed higher selectivity than the standard drug moclobemide. According to the experimental K(i) values, compounds 6i, 6d, and 6a exhibited the highest inhibitory activity toward hMAO-A. The AutoDock 4.2 program was employed to perform automated molecular docking. The calculated results obtained computationally were in good agreement with the experimental values.
authors: Analysis and Control Laboratories of General Directorate of Pharmaceuticals and Pharmacy, Ministry of Health of Turkey, Sıhhiye, Ankara, Turkey.
authors: Begüm
authors: B
authors: Evranos-Aksöz
authors: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors: İpek
authors: İ
authors: Baysal
authors: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors: Samiye
authors: S
authors: Yabanoğlu-Çiftçi
authors: Department of Bioinformatics and Genetics (Head) Cibali Campus, Faculty of Engineering and Natural Sciences, Kadir Has University, Fatih, Istanbul, Turkey.
authors: Teodora
authors: T
authors: Djikic
authors: Department of Bioinformatics and Genetics (Head) Cibali Campus, Faculty of Engineering and Natural Sciences, Kadir Has University, Fatih, Istanbul, Turkey.
authors: Kemal
authors: K
authors: Yelekçi
authors: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors: Gülberk
authors: G
authors: Uçar
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey.
authors: Rahmiye
authors: R
authors: Ertan
mesh_terms: D015195:Drug Design; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D020912:Moclobemide / Q000494:pharmacology; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011487:Protein Conformation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006835:Hydrazones; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; D020912:Moclobemide
keywords: 2-Pyrazoline; Hydrazone; MAO inhibitors; Molecular docking