title: Potent Selective Inhibition of Monoamine Oxidase A by Alternariol Monomethyl Ether Isolated fromAlternaria brassicae.
abstract: Alternariol monomethyl ether (AME), a dibenzopyrone derivative, was isolated fromAlternaria brassicaealong with altertoxin II (ATX-II). The compounds were tested for the inhibitory activity of monoamine oxidase (MAO), which catalyzes neurotransmitting monoamines. AME was found to be a highly potent and selective inhibitor of human MAO-A with an IC50value of 1.71 µM; however, it was found to be ineffective for MAO-B inhibition. ATX-II was not effective for the inhibition of either MAO-A or MAO-B. The inhibition of MAO-A using AME was apparently instantaneous. MAO-A activity was almost completely recovered after the dilution of the inhibited enzyme with an excess amount of AME, suggesting AME is a reversible inhibitor. AME showed mixed inhibition for MAO-A in Lineweaver-Burk plots with aKivalue of 0.34 µM. The findings of this study suggest that microbial metabolites and dibenzopyrone could be potent MAO inhibitors. In addition, AME could be a useful lead compound for developing reversible MAO-A inhibitors to treat depression, Parkinson's disease, and Alzheimer's disease.
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: Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Yeon Ji
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Republic of Korea.
authors.forename: Sang-Jip
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Kim
mesh_terms: D000528:Alternaria / Q000737:chemistry* / Q000201:enzymology; D000544:Alzheimer Disease / Q000188:drug therapy; D001551:Benz(a)Anthracenes / Q000737:chemistry / Q000302:isolation & purification; D003863:Depression / Q000188:drug therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy
chemical_list: D001551:Benz(a)Anthracenes; D007783:Lactones; D008996:Monoamine Oxidase Inhibitors; C050234:altertoxin II; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C018206:alternariol monomethyl ether
keywords: Alternaria brassicae; Alternariol monomethyl ether; mixed inhibition; monoamine oxidase; selective inhibitor