Potent inhibition of monoamine oxidase b by a piloquinone from marine-derived streptomyces sp. CNQ-027

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 lead_i compounds for developing MAO enzyme inhibitors to treat related disorders, such as depression, Parkinson’s disease, and Alzheimer’s disease.