An investigation of the monoamine oxidase inhibition properties of benzothiazole derivatives

Literature reports that alkyloxy substituted coumarin derivatives inhibit the monoamine oxidase (MAO) enzymes, specifically the MAO-B isoform. To further investigate this finding, the present study synthesised and evaluated a series of alkyloxy substituted benzothiazole derivatives as potential inhibitors of human MAO-A and MAO-B. The results showed that 6-((4-nitrobenzyl)oxy)benzo[ d ]thiazole ( 1f ) was the most potent MAO-A inhibitor with an IC 50 value of 0.336 μM, while the most potent MAO-B inhibitors were 6-((3-chlorobenzyl)oxy)benzo[ d ]thiazole ( 1e ) and 4-((benzo[ d ]thiazol-6-yloxy)methyl)benzonitrile ( 1i ), which both demonstrated IC 50 values of 0.0028 μM. For comparison, the reference MAO-A and MAO-B inhibitors, toloxatone and safinamide, exhibited IC 50 values of 1.67 and 0.240 μM, respectively. Potential binding modes and interactions of the inhibitors with MAO were proposed with molecular docking. This study concluded that the benzothiazole derivatives were potent and specific MAO-B inhibitors. Inhibitors of MAO-A are used to treat neuropsychiatric disorders (e.g., depression and anxiety disorder), while MAO-B inhibitors are established therapy for Parkinson's disease. • Benzothiazole derivatives were investigated as inhibitors of human MAO • The most potent MAO-A inhibitor presented with an IC 50 of 0.336 μM • The most potent MAO-B inhibitors presented with IC 50 of 0.0028 μM • The benzothiazole derivatives were potent and specific MAO-B inhibitors • MAO-B inhibitors are established therapy for Parkinson's disease