Novel 1,3,4-thiadiazole compounds as potential MAO-A inhibitors - design, synthesis, biological evaluation and molecular modelling.

Monoamine oxidases (MAOs) are important drug targets for the management of neurological disorders. Herein, a series of new 1,3,4-thiadiazole derivatives bearing various alkyl/arylamine moieties as MAO inhibitors were designed and synthesized. All of the compounds were more selective against MAO-A than MAO-B. The half maximal inhibitory concentration (IC) values of most of the compounds were lower than that of the common drug moclobemide (IC = 4.664 μM) and compound was proven to be the most active compound (IC = 0.060 μM). Moreover, it was seen that compound showed a similar inhibition profile to that of clorgyline (IC = 0.048 μM). The inhibition profile was found to be reversible and competitive for compound with MAO-A selectivity. Molecular modelling studies aided in the understanding of the interaction modes between compound and MAO-A. Furthermore, this compound was predicted to have a good pharmacokinetic profile and high BBB penetration. Therefore, such compounds are of interest towards developing new MAO inhibitors.