Medicarpin and Homopterocarpin Isolated from Canavalia lineata as Potent and Competitive Reversible Inhibitors of Human Monoamine Oxidase-B.

Thirteen compounds were isolated from the pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds (medicarpin) and (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except (prunetin) and . Compounds and were reversible competitive inhibitors against hMAO-B (K = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of . However, the 9-OCH3 group at B-ring of showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of (pterocarpin). In cytotoxicity study, and showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of and for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds and be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders.