Imidazole bearing chalcones as a new class of monoamine oxidase inhibitors

In the present study, series of eleven (2E) 1 [4 (1H imidazol-1-yl)substituted phenyl]-3-phenylprop-2- en-1-one(IM1-IM11) derivatives were synthesized and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. The results indicate that (2E)-3-[4 (dimethylamino) phenyl]-1-[4-(1H-imidazol-1-yl) phenyl] prop-2-en-1-one (IM5) is a nonselective and reversible competitive inhibitor of MAO-A and MAO-B with IC50 values of 0.30 +/- 0.010 and 0.40 +/- 0.017 mu M, respectively ; those of (2E)-1-[4 (1H imidazol-1-yl) phenyl]3-(4-methylphenyl) prop-2-en-1-one (IM4) were 1.06 +/- 0.090 and 0.32 +/- 0.021 mu M, respectively. Kinetic studies document that both IM5 and IM4 are competitive inhibitors of MAO-A and MAO-B with Ki value of 0.11 +/- 0.0085 and 0.085 +/- 0.0064 mu M, respectively. Molecular docking studies of lead compounds further explained the binding modes in the inhibitor binding cavity of both MAO-A and MAO-B.