Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i>
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 <i>Daldinia fissa</i>) extract showed the highest inhibitory...
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2309-608X/7/2/84 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Geum-Seok Jeong |
| collection | DOAJ |
| description | 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 <i>Daldinia fissa</i>) 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 (IC<sub>50</sub> = 3.23 µM) compared to MAO-A (IC<sub>50</sub> = 13.97 µM). HMC is a reversible competitive inhibitor with a K<sub>i</sub> 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. |
| first_indexed | 2024-03-09T03:35:36Z |
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| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T03:35:36Z |
| publishDate | 2021-01-01 |
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| series | Journal of Fungi |
| spelling | doaj.art-7e77930387b14d3dba79c20a6fc6281b2023-12-03T14:48:40ZengMDPI AGJournal of Fungi2309-608X2021-01-01728410.3390/jof7020084Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i>Geum-Seok Jeong0Myung-Gyun Kang1Sang-Ah Han2Ji-In Noh3Jong-Eun Park4Sang-Jip Nam5Daeui Park6Sung-Tae Yee7Hoon Kim8Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaCollege of Pharmacy, Ewha Womans University, Seoul 03760, KoreaDepartment of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, KoreaDepartment of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, KoreaDepartment of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, KoreaDepartment of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, KoreaDepartment of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, KoreaInhibitory 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 <i>Daldinia fissa</i>) 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 (IC<sub>50</sub> = 3.23 µM) compared to MAO-A (IC<sub>50</sub> = 13.97 µM). HMC is a reversible competitive inhibitor with a K<sub>i</sub> 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.https://www.mdpi.com/2309-608X/7/2/84endogenous lichen fungus<i>Daldinia fissa</i>5-hydroxy-2-methyl-chroman-4-oneselective monoamine oxidase B inhibitorblood–brain barrier permeabilitydocking simulation |
| spellingShingle | 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 Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i> Journal of Fungi endogenous lichen fungus <i>Daldinia fissa</i> 5-hydroxy-2-methyl-chroman-4-one selective monoamine oxidase B inhibitor blood–brain barrier permeability docking simulation |
| title | Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i> |
| title_full | Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i> |
| title_fullStr | Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i> |
| title_full_unstemmed | Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i> |
| title_short | Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus <i>Daldinia fissa</i> |
| title_sort | selective inhibition of human monoamine oxidase b by 5 hydroxy 2 methyl chroman 4 one isolated from an endogenous lichen fungus i daldinia fissa i |
| topic | endogenous lichen fungus <i>Daldinia fissa</i> 5-hydroxy-2-methyl-chroman-4-one selective monoamine oxidase B inhibitor blood–brain barrier permeability docking simulation |
| url | https://www.mdpi.com/2309-608X/7/2/84 |
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