Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus Daldinia fissa.

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

doi:10.3390/jof7020084

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.

Highlights

Lichens are complex life forms in which algae and fungi maintain a symbiotic relationship
Endogenous Lichen Fungi 13 (ELF13) was selected for further study and subjected to the cultivation, extraction, and isolation of the monoamine oxidases (MAOs)-B inhibitor
ELF13 was identified as a fungus Daldinia fissa forming a symbiotic relationship with the lichen Thamnolia vermicularis (Sw.) Schaer

Summary

Introduction

Lichens are complex life forms in which algae and fungi maintain a symbiotic relationship. They live in extreme environments, such as tundra, desert, and volcanic areas in the polar regions, and grow in various places, such as rainforests and temperate regions [1]. Alzheimer’s disease (AD) is the most common degenerative brain disease that causes dementia [6]. It develops very slowly and is characterized by a gradual progression. The number of patients with AD is increasing each year worldwide; it is important to identify an effective way to treat AD

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