Selective inhibition of monoamine oxidase A by hispidol

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 K_i 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 (K_i?= 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.