TY - JOUR
T1 - Chromenone derivatives as monoamine oxidase inhibitors from marine-derived MAR4 clade Streptomyces sp. CNQ-031
AU - Oh, Jong Min
AU - Lee, Chaeyoung
AU - Nam, Sang Jip
AU - Kim, Hoon
N1 - Funding Information:
This study was supported by the National Research Foundation of Korea (NRF) grant No. NRF-2019R1A2C1088967, funded by the Korean government of the Republic of Korea.
Publisher Copyright:
Copyright© 2021 by The Korean Society for Microbiology and Biotechnology
PY - 2021/7/28
Y1 - 2021/7/28
N2 - Three compounds were isolated from marine-derived Streptomyces sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC50) of 2.70 μM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC50 of 3.42 μM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The Ki value of compound 1 for MAO-A was 0.94 ± 0.28 μM, and the Ki values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 μM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer’s disease.
AB - Three compounds were isolated from marine-derived Streptomyces sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC50) of 2.70 μM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC50 of 3.42 μM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The Ki value of compound 1 for MAO-A was 0.94 ± 0.28 μM, and the Ki values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 μM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer’s disease.
KW - Chromenone derivatives
KW - Monoamine oxidases
KW - Reversible competitive inhibitors
KW - Streptomyces sp. CNQ-031
UR - http://www.scopus.com/inward/record.url?scp=85111848652&partnerID=8YFLogxK
U2 - 10.4014/jmb.2105.05003
DO - 10.4014/jmb.2105.05003
M3 - Article
C2 - 34099598
AN - SCOPUS:85111848652
SN - 1017-7825
VL - 31
SP - 1022
EP - 1027
JO - Journal of Microbiology and Biotechnology
JF - Journal of Microbiology and Biotechnology
IS - 7
ER -