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

Abstract

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 on BB-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, compounds 4i and 4t achieved IC50 values of 0.041 ± 0.001 µM and 0.065 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition by compounds 4i and 4t was studied using Lineweaver–Burk plot. The nature of inhibition was also determined to be non-competitive. Cytotoxicity tests were conducted and compounds 4i and 4t were found to be non-toxic. Molecular docking studies were also carried out for compound 4i, which was found as the most potent agent, within hMAO-B catalytic site.