Selective inhibition of monoamine oxidase A by hispidol

Abstract

Hispidol, an aurone, isolated from Glycine max Merrill, was found to potently and selectively inhibit an isoform of recombinant human monoamine oxidase-A (MAO-A), with an IC50 value of 0.26 μM, and to inhibit MAO-B, but with lower potency (IC50 = 2.45 μM). Hispidol reversibly and competitively inhibited MAO-A with a Ki value of 0.10 μM with a potency much greater than toloxatone (IC50 = 1.10 μM), a marketed drug. It also reversibly and competitively inhibited MAO-B (Ki = 0.51 μM). Sulfuretin, an analog of hispidol, effectively inhibited MAO-A (IC50 = 4.16 μM) but not MAO-B (IC50 > 80 μM). A comparison of their chemical structures showed that the 3′-hydroxyl group of sulfuretin might reduce its inhibitory activities against MAO-A and MAO-B. Flexible docking simulation revealed that the binding affinity of hispidol for MAO-A (-9.1 kcal/mol) was greater than its affinity for MAO-B (-8.7 kcal/mol). The docking simulation showed hispidol binds to the major pocket of MAO-A or MAO-B. The findings suggest hispidol is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a novel lead compound for development of novel reversible inhibitors of MAO-A