3-(E)-Styryl-2H-chromene derivatives as potent and selective monoamine oxidase B inhibitors.

A series of novel 3-(E)-styryl-2H-chromene derivatives were synthesized and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. All compounds exhibited no inhibitory activity towards MAO-A at 10 μM whereas compounds 1-5, 7, 9, 11-13, 15 and 16 showed strong inhibitory activity towards MAO-B at this concentration. Of these, compound 3, which contains fluorine at R, showed the highest activity (IC = 10 nM), and is about 22-fold more potent than pargyline (used as a positive control). Quantitative structure-activity relationship (QSAR) analyses of 3-(E)-styryl-2H-chromene derivatives were conducted using Molecular Operating Environment (MOE). QSAR analyses of 3-(E)-styryl-2H-chromene derivatives with pIC values for MAO-B demonstrated that 140 descriptors showed significant correlations. The strongly correlated descriptors indicated that properties such as molecular shape, size, and hydrophobicity, as well as the functional groups, of 3-(E)-styryl-2H-chromene derivatives are important for their inhibitory activity. This is the first report identifying 3-(E)-styryl-2H-chromene derivatives as potent and selective MAO-B inhibitors. These results suggest that the 3-(E)-styryl-2H-chromene structure may be a useful scaffold for the design and development of novel monoamine oxidase inhibitors.