Synthesis of some benzothiazole-piperazine derivatives, investigation by in vitro and molecular modelling for hMAO inhibitory activities

Monoamine oxidase (MAO) is an enzyme that helps regulate the functions of intracellular amines, as well as chemicals such as dopamine, serotonin and norepinephrine, in the brain and its tissues. Active substances that are inhibitors of monoamine oxidases (MAOs) are used in the treatment of anxiety, depression and Alzheimer’s disease. Previous studies have shown that compounds containing piperazine rings show MAO-A inhibitory activity. Based on these studies, 4 compounds containing piperazine and benzothiazole rings were designed, and the structures of the compounds were elucidated using spectroscopic methods such as HRMS and 1H-NMR. hMAO-A and hMAO-B inhibitory activity was examined by in vitro methods. An in silico procedure was applied to investigate the residues and binding modes that interact with the docking of compounds 3a-d to the active site of the hMAO-A (PDB ID: 2Z5X) enzyme identified in the previous study. Compound 3b was found to be the most effective agent among the synthesized compounds with an IC50 value of 0.104±0.004 µM against the MAO-A enzyme.