Design, synthesis and biological evaluation of novel benzocoumarin derivatives as potent inhibitors of MAO-B activity

[Display omitted] •Novel benzo[g]coumarins and benzo[h]coumarins synthesized.•A6 displayed the most potent MAO-B inhibitory activity with IC50 value of 13 nM.•Inhibition mode of A6 determined as mixed inhibition with a Ki value of 3.274 nM.•Binding mode predicted using molecular docking.•Anti-bacterial activities of the compounds were also determined. The continued research of novel reversible inhibitors targeting monoamine oxidase (MAO) B remains crucial for effectively symptomatic treatment of Parkinson’s disease. In this study we synthesized and evaluated a new series of 3-aryl benzo[g] and benzo[h] coumarin derivatives as MAO-B inhibitors. Compound A6 has been found to display the most potent inhibitory activity and selectivity against the MAO-B isoform (IC50 = 13 nM and SI = >7693.31 respectively). Inhibition mode of A6 on MAO-B was predicted as mixed reversible inhibition with a Ki value of 3.274 nM. Furthermore, in order to elaborate structure–activity relationships, the binding mode of A6 was investigated by molecular docking simulations.