Selective inhibition of human monoamine oxidase B by 5-hydroxy-2-methyl-chroman-4-one isolated from an endogenous lichen fungus Daldinia fissa

Geum Seok Jeong, Myung Gyun Kang, Sang Ah Han, Ji In Noh, Jong Eun Park, Sang Jip Nam, Daeui Park, Sung Tae Yee, Hoon Kim

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish
Article number84
Pages (from-to)1-16
Number of pages16
JournalJournal of Fungi
Volume7
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • 5-hydroxy-2-methyl-chroman-4-one
  • Blood-brain barrier permeability
  • Daldinia fissa
  • Docking simulation
  • Endogenous lichen fungus
  • Selective monoamine oxidase B inhibitor

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