title: Potent selective monoamine oxidase B inhibition by maackiain, a pterocarpan from the roots of Sophora flavescens.
abstract: Monoamine oxidase (MAO) catalyzes the oxidation of monoamines and its two isoforms, MAO-A and MAO-B, break down neurotransmitter amines. Of the compounds isolated from the roots of Sophora flavescens, (-)-maackiain (4), a pterocarpan, was found to potently and selectively inhibit human MAO-B, with an IC50 of 0.68μM, and to have a selectivity index of 126.2 for MAO-B. As compared with other herbal natural products, the IC50 value of 4 for MAO-B is one of the lowest reported to date. Genistein (1) highly, effectively and non-selectively inhibited MAO-A and MAO-B with IC50 values of 3.9μM and 4.1μM, respectively. (-)-4-Hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (2) effectively and non-selectively inhibited MAO-A and MAO-B with IC50 values of 20.3μM and 10.3μM, respectively. In addition, compound 4 reversibly and competitively inhibited MAO-B with a Ki value of 0.054μM. Molecular docking simulation revealed that the binding affinity of 4 for MAO-B (-26.6kcal/mol) was greater than its affinity for MAO-A (-8.3kcal/mol), which was in-line with our inhibitory activity findings. Furthermore, Cys172 of MAO-B was found to be a key residue for hydrogen bonding with compound 4. The findings of this study suggest compound 4 be viewed as a new potent, selective, and reversible MAO-B inhibitor, and that compounds 1 and 2 be considered useful lead compounds for the developments of nonselective and reversible MAO inhibitors for the treatment of disorders like Parkinson's disease, Alzheimer disease, and depression.
authors: Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
authors: Hyun Woo
authors: HW
authors: Lee
authors: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
authors: Hyung Won
authors: HW
authors: Ryu
authors: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors: Myung-Gyun
authors: MG
authors: Kang
authors: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors: Daeui
authors: D
authors: Park
authors: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
authors: Sei-Ryang
authors: SR
authors: Oh
authors: Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea. Electronic address: hoon@sunchon.ac.kr.
authors: Hoon
authors: H
authors: Kim
mesh_terms: D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D036343:Pterocarpans / Q000494:pharmacology*; D029909:Sophora / Q000737:chemistry; D000094162:Phytoalexins
chemical_list: D008995:Monoamine Oxidase; D008996:Monoamine Oxidase Inhibitors; D036343:Pterocarpans; C001449:inermin; D000094162:Phytoalexins
keywords: 4-Hydroxy-3-methoxy-8,9-methylenedioxypterocarpan; Human monoamine oxidase; Maackiain; Molecular docking; Selective competitive inhibitor; Sophora flavescens