Synthesis,in vitroenzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors

Many studies have been conducted on the selective inhibition of human monoamine oxidase B (hMAO-B) enzyme using benzylamine-sulphonamide derivatives. Using various chemical modifications onBB-4h, which was reported previously by our team and showed a significant level of MAO-B inhibition, novel benzylamine-sulphonamide derivatives were designed, synthesised, and their MAO inhibition potentials were evaluated. Among the tested derivatives, compounds4iand4tachieved IC(50)values of 0.041 +/- 0.001 mu M and 0.065 +/- 0.002 mu M, respectively. The mechanism ofhMAO-B inhibition by compounds4iand4twas studied using Lineweaver-Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds4iand4twere found to be non-toxic. Molecular docking studies were also carried out for compound4i, which was found as the most potent agent, withinhMAO-B catalytic site.