Selective inhibition of human monoamine oxidase B by 5-hydroxy-2-methyl-chroman-4-one isolated from an endogenous lichen fungus Daldinia fissa
- 주제(키워드) 5-hydroxy-2-methyl-chroman-4-one , Blood-brain barrier permeability , Daldinia fissa , Docking simulation , Endogenous lichen fungus , Selective monoamine oxidase B inhibitor
- 등재 SCIE, SCOPUS
- 발행기관 MDPI AG
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175687
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/jof7020084
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) and antioxidant activity were evaluated for 195 extracts from Ukraine-derived endogenous lichen fungi (ELF). Among them, an ELF13 (identified as Daldinia fissa) extract showed the highest inhibitory activity against MAO-B, and 5-hydroxy-2-methyl-chroman-4-one (HMC) was isolated as a ~ 4-fold selective inhibitor of MAO-B (IC50 = 3.23 µM) compared to MAO-A (IC50 = 13.97 µM). HMC is a reversible competitive inhibitor with a Ki value of 0.896 µM. No cytotoxicity was observed in normal and cancer cells at 50 µM of HMC. HMC showed blood-brain barrier permeability and high gastrointestinal absorption in silico pharmacokinetics. The docking simulation results showed that the binding affinity of HMC for MAO-B (-7.3 kcal/mol) was higher than that of MAO-A (-6.1 kcal/mol) and that HMC formed a hydrogen bond interaction with Cys172 of MAO-B (distance: 3.656 Å), whereas no hydrogen bonding was predicted with MAO-A. These results suggest that HMC can be considered a candidate for the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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