title: Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-DerivedStreptomycessp. CNQ-027.
abstract: Two piloquinone derivatives isolated fromStreptomycessp. CNQ-027 were tested for the inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1-oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of human MAO-B, with an IC50value of 1.21 µ; in addition, it was found to be highly effective against MAO-A, with an IC50value of 6.47 µ. Compound 1 was selective, but not extremely so, for MAO-B compared with MAO-A, with a selectivity index value of 5.35. Compound 1,8-dihydroxy-2-methyl-3-(4-methyl-1-oxopentyl)-9,10-phenanthrenedione (2) was moderately effective for the inhibition of MAO-B (IC50= 14.50 µ) but not for MAO-A (IC50> 80 µ). There was no time-dependency in inhibition of MAO-A or -B by compound 1, and the MAO-A and -B activities were almost completely recovered in the dilution experiments with an excess amount of compound 1. Compound 1 showed competitive inhibition for MAO-A and -B, withKivalues of 0.573 and 0.248 µ, respectively. These results suggest that piloquinones from a microbial source could be potent reversible MAO inhibitors and may be useful lead compounds for developing MAO enzyme inhibitors to treat related disorders, such as 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: Hansol
authors.initials: H
authors.lastname: Choi
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: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0204, USA.
authors.forename: William
authors.initials: W
authors.lastname: Fenical
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: D003863:Depression / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013302:Streptomyces / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D012336:RNA, Ribosomal, 16S; D008995:Monoamine Oxidase
keywords: Monoamine oxidase; Streptomyces sp. CNQ-027; competitive inhibitor; piloquinone; potent selective inhibitor