Design and Synthesis of New Benzothiazole Compounds as Selective hMAO-B Inhibitors.

In the current work a new class of novel benzothiazole-hydrazone derivatives was designed and synthesized as MAO-B inhibitors. Structures of the obtained compounds (-) were characterized by IR, ¹H-NMR, C-NMR, and HRMS spectroscopic methods. The inhibitory activity of compounds (-) against MAO-A and MAO-B enzymes was evaluated by using an in vitro fluorometric method. According to activity results, some of the synthesized compounds displayed selective and significant MAO-B enzyme inhibitor activity. Compound was the most active derivative in the series with an IC value of 0.060 µM. Furthermore, cytotoxicity of compound 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. Bınding modes between the most active compound and the MAO-B enzyme were analyzed by docking studies. It was observed that there is a strong interaction between compound and enzyme active site.