Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces sp CNQ-027

TitlePotent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces sp CNQ-027
Publication TypeJournal Article
Year of Publication2017
AuthorsLee H.W, Choi H., Nam SJ, Fenical W, Kim H
JournalJournal of Microbiology and Biotechnology
Volume27
Pagination785-790
Date Published2017/04
Type of ArticleArticle
ISBN Number1017-7825
Accession NumberWOS:000401123000017
Keywordscompetitive inhibitor; drug discovery; mao-b; Monoamine oxidase; natural-products; piloquinone; potent; roots; selective inhibitor; Streptomyces sp CNQ-027
Abstract

Two piloquinone derivatives isolated from Streptomyces sp. 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 IC50 value of 1.21 mu M; in addition, it was found to be highly effective against MAO-A, with an IC50 value of 6.47 mu M. 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 mu M) but not for MAO-A (IC50 > 80 mu M). 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, with K-i values of 0.573 and 0.248 mu M, 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.

DOI10.4014/jmb.1612.12025
Short TitleJ. Microbiol. Biotechnol.
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