TY - JOUR
T1 - Potent inhibition of monoamine oxidase b by a piloquinone from marine-derived streptomyces sp. CNQ-027
AU - Lee, Hyun Woo
AU - Choi, Hansol
AU - Nam, Sang Jip
AU - Fenical, William
AU - Kim, Hoon
N1 - Publisher Copyright:
© 2017 by The Korean Society for Microbiology and Biotechnology.
PY - 2017/4
Y1 - 2017/4
N2 - 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.
AB - 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.
KW - Competitive inhibitor
KW - Monoamine oxidase
KW - Piloquinone
KW - Potent selective inhibitor
KW - Streptomyces sp. CNQ-027
UR - http://www.scopus.com/inward/record.url?scp=85018258481&partnerID=8YFLogxK
U2 - 10.4014/jmb.1612.12025
DO - 10.4014/jmb.1612.12025
M3 - Article
C2 - 28068665
AN - SCOPUS:85018258481
SN - 1017-7825
VL - 27
SP - 785
EP - 790
JO - Journal of Microbiology and Biotechnology
JF - Journal of Microbiology and Biotechnology
IS - 4
ER -