Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Chromenone Derivatives as Monoamine Oxidase Inhibitors from Marine-Derived MAR4 Clade Streptomyces sp. CNQ-031

  • Oh, Jong Min (Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University) ;
  • Lee, Chaeyoung (Graduate School of Industrial Pharmaceutical Sciences, Ewha Womans University) ;
  • Nam, Sang-Jip (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Kim, Hoon (Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University)
  • Received : 2021.05.04
  • Accepted : 2021.05.27
  • Published : 2021.07.28
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Abstract

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.

Keywords

Acknowledgement

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.

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