Potent inhibition of monoamine oxidase b by a piloquinone from marine-derived 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 IC value of 1.21 µM; in addition, it was found to be highly effective against MAO-A, with an IC value of 6.47 µM. Compound 1 was selective, but not extremely50 so, for MAO-B compared with50 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 (IC = 14.50 µM) but not for MAO-A (IC > 80 µM). There was no time-dependency in inhibition50 of MAO-A or -B by compound 1, and50the 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 values of 0.573 and 0.248 µM, respectively. These results suggest that piloquinones from a microbial source could be potent reversible MAO inhibitors and may be useful leadi compounds for developing MAO enzyme inhibitors to treat related disorders, such as depression, Parkinson’s disease, and Alzheimer’s disease. © 2017 by The Korean Society for Microbiology and Biotechnology.