Design, Synthesis and Biological Evaluation of Novel N-Pyridyl-Hydrazone Derivatives as Potential Monoamine Oxidase (MAO) Inhibitors.

A new series of N-pyridyl-hydrazone derivatives was synthesized by using a simple and efficient method. The final compounds obtained were screened for their inhibitory potency against monoamine oxidase (MAO) A and B. The newly synthesized compounds 2a-2n specifically inhibited monoamine oxidases, displaying notably low IC50 values. Compounds 2i and 2j, with a CF₃ and OH group on the 4-position of the phenyl ring, respectively, showed considerable MAO-A and MAO-B inhibitory activities. Compounds 2k, 2l and 2n, with N-methylpyrrole, furan and pyridine moieties instead of the phenyl ring, were the most powerful and specific inhibitors of MAO-A, with IC50 values of 6.12 μM, 10.64 μM and 9.52 μM, respectively. Moreover, these active compounds were found to be non-cytotoxic to NIH/3T3 cells. This study supports future studies aimed at designing MAO inhibitors to obtain more viable medications for neurodegenerative disorders, such as Parkinson's disease.