title: Selective inhibition of monoamine oxidase A by purpurin, an anthraquinone.
abstract: Monoamine oxidase (MAO) catalyzes the oxidation of monoamines that act as neurotransmitters. During a target-based screening of natural products using two isoforms of recombinant human MAO-A and MAO-B, purpurin (an anthraquinone derivative) was found to potently and selectively inhibit MAO-A, with an IC50value of 2.50μM, and not to inhibit MAO-B. Alizarin (also an anthraquinone) inhibited MAO-A less potently with an IC50value of 30.1μM. Furthermore, purpurin was a reversible and competitive inhibitor of MAO-A with a Kivalue of 0.422μM. A comparison of their chemical structures suggested the 4-hydroxy group of purpurin might play an important role in its inhibition of MAO-A. Molecular docking simulation showed that the binding affinity of purpurin for MAO-A (-40.0kcal/mol) was higher than its affinity for MAO-B (-33.9kcal/mol), and that Ile 207 and Gly 443 of MAO-A were key residues for hydrogen bonding with purpurin. The findings of this study suggest purpurin is a potent, selective, reversible inhibitor of MAO-A, and that it be considered a new potential lead compound for development of novel reversible inhibitors of MAO-A (RIMAs).
authors.affiliation: Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors.forename: Myung-Gyun
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.affiliation: Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: 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.forename: Hoon
authors.initials: H
authors.lastname: Kim
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D008995:Monoamine Oxidase / Q000737:chemistry / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase; C511975:purpurin anthraquinone
keywords: Competitive inhibitor; Molecular docking; Monoamine oxidase A; Purpurin; Selective inhibitor