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.

摘要

使用苄胺-磺酰胺衍生物选择性抑制人单胺氧化酶B（h MAO-B）酶已进行了许多研究。我们的团队先前报道了对BB-4h的各种化学修饰，显示出对MAO-B的显着抑制作用，设计，合成了新型苄胺-磺酰胺衍生物，并评估了其对MAO的抑制潜力。在测试的衍生物中，化合物4i和4t的IC ₅₀值分别为0.041±0.001 µM和0.065±0.002 µM。化合物4i和4t抑制h MAO-B的机理使用Lineweaver–Burk图进行了研究。抑制的性质也被确定为非竞争性的。进行了细胞毒性测试，发现化合物4i和4t无毒。还对化合物4i（在h MAO-B催化位点内被发现是最有效的试剂）进行了分子对接研究。