Potent and selective MAO-B inhibitory activity: Amino- versus nitro-3-arylcoumarin derivatives

In this study we synthesized and evaluated a new series of amino and nitro 3-arylcoumarins as hMAO-A and hMAO-B inhibitors. Compounds 2, 3, 5 and 6 presented a better activity and selectivity profile against the hMAO-B isoform (IC50 values between 2 and 6 nM) than selegiline. In general, the amino derivatives (4–6) proved to be more selective against MAO-B than the nitro derivatives (1–3). Additionally, a theoretical study of some physicochemical properties, PAMPA and reversibility assays for the most potent derivative, and molecular docking simulations were carried out to further explain the pharmacological results, and to identify the hypothetical binding mode for the compounds inside the hMAO-B.

Graphical abstractThe current work describes the synthesis, hMAO-A and hMAO-B in vitro inhibition, parallel artificial membrane permeation assay (PAMPA-BBB), reversibility assay, theoretical study of some physicochemical properties and docking calculations of a selected series of amino/nitro-3-arylcoumarins as potent and selective MAO-B inhibitors.Figure optionsDownload full-size imageDownload as PowerPoint slide