MOLECULES, vol.22, no.12, 2017 (SCI-Expanded)
In the current work a new class of novel benzothiazole-hydrazone derivatives was designed and synthesized as hMAO-B inhibitors. Structures of the obtained compounds (3a-3j) were characterized by IR, 1H-NMR, 13C-NMR, and HRMS spectroscopic methods. The inhibitory activity of compounds (3a-3j) against hMAO-A and hMAO-B enzymes was evaluated by using an in vitro fluorometric method. According to activity results, some of the synthesized compounds displayed selective and significant hMAO-B enzyme inhibitor activity. Compound 3e was the most active derivative in the series with an IC50 value of 0.060 mu M. Furthermore, cytotoxicity of compound 3e was investigated and found to be non-cytotoxic. Absorption, distribution, metabolism, and excretion (ADME) and blood-brain barrier (BBB) permeability predictions were performed for all compounds. It was determined that these compounds may have a good pharmacokinetic profiles. Bnding modes between the most active compound 3e and the hMAO-B enzyme were analyzed by docking studies. It was observed that there is a strong interaction between compound 3e and enzyme active site.