Monoamine Oxidase Inhibitory Activity of Novel Pyrazoline Analogues: Curcumin Based Design and Synthesis

A series of new 2-methoxy-4-(5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)­phenolderivatives, 4–13, were synthesized and tested for their human MAO inhibitory activity. All the compounds were found to be selective and reversible toward hMAO-A except 4, a selective inhibitor of hMAO-B and 12, a nonselective inhibitor. Compound 7 was found to be a potent inhibitor of hMAO-A with K_i = 0.06 ± 0.003 μM and was having selectivity index of (SI = 1.02 × 10^–5). It was found to be better than standard drug, Moclobemide (hMAO-A with K_i = 0.11 ± 0.01 μM) with selectivity index of SI = 0.049. Molecular docking simulation was carried out to understand the crucial interactions responsible for selectivity and potency.