Chromenone Derivatives as Monoamine Oxidase Inhibitors from Marine-Derived MAR4 Clade Streptomyces sp. CNQ-031
- 주제(키워드) Monoamine oxidases , chromenone derivatives , Streptomyces sp , CNQ-031 , reversible competitive inhibitors
- 주제(기타) Biotechnology & Applied Microbiology
- 주제(기타) Microbiology
- 설명문(일반) [Oh, Jong Min; Kim, Hoon] Sunchon Natl Univ, Dept Pharm & Res Inst Life Pharmaceut Sci, Sunchon 57922, South Korea; [Lee, Chaeyoung] Ewha Womans Univ, Grad Sch Ind Pharmaceut Sci, Seoul 03760, South Korea; [Nam, Sang-Jip] Ewha Womans Univ, Dept Chem & Nanosci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS, KCI등재
- 발행기관 KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182352
- 본문언어 영어
- Published As http://dx.doi.org/10.4014/jmb.2105.05003
초록/요약
Three compounds were isolated from marine-derived Streptomyces sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-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 mu M 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 mu M 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 K-i value of compound 1 for MAO-A was 0.94 +/- 0.28 mu M, and the K-i values of compound 2 for MAO-A and MAO-B were 3.57 +/- 0.60 and 1.89 +/- 0.014 mu M, 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.
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