Synthesis and Screening of Human Monoamine Oxidase-A Inhibitor Effect of New 2-Pyrazoline and Hydrazone Derivatives

Abstract

A group of 35-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 H-1 NMR C-13 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.