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Potent and Selective Inhibitors of Human Monoamine Oxidase A from an Endogenous Lichen Fungus Diaporthe mahothocarpus

Title
Potent and Selective Inhibitors of Human Monoamine Oxidase A from an Endogenous Lichen Fungus Diaporthe mahothocarpus
Authors
Jeong, Geum SeokHillman, Prima F.Kang, Myung-GyunHwang, SungboPark, Jong-EunNam, Sang-JipPark, DaeuiKim, Hoon
Ewha Authors
남상집
SCOPUS Author ID
남상집scopusscopus
Issue Date
2021
Journal Title
JOURNAL OF FUNGI
ISSN
2309-608XJCR Link
Citation
JOURNAL OF FUNGI vol. 7, no. 10
Keywords
endogenous lichen fungusDiaporthe mahothocarpusalternariol5-hydroxy-alternariolmycoepoxydieneselective monoamine oxidase A inhibitordocking simulation
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Using 126 endogenous lichen fungus (ELF) extracts, inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) were evaluated. Among them, extract ELF29 of the endogenous fungus Diaporthe mahothocarpus of the lichen Cladonia symphycarpia showed the highest inhibitory activity against hMAO-A. Compounds alternariol (AT), 5 & PRIME;-hydroxy-alternariol (HAT), and mycoepoxydiene (MED), isolated from the extract, had potent inhibitory activities against hMAO-A with IC50 values of 0.020, 0.31, and 8.68 mu M, respectively. AT, HAT, and MED are reversible competitive inhibitors of hMAO-A with K-i values of 0.0075, 0.116, and 3.76 mu M, respectively. The molecular docking studies suggested that AT, HAT, and MED had higher binding affinities for hMAO-A (-9.1, -6.9, and -5.6 kcal/mol, respectively) than for hMAO-B (-6.3, -5.2, and -3.7 kcal/mol, respectively). The relative tight binding might result from a hydrogen bond interaction of the three compounds with a Tyr444 residue in hMAO-A, whereas no hydrogen bond interaction was proposed in hMAO-B. In silico pharmacokinetics, the three compounds showed high gastrointestinal absorption without violating Lipinski's five rules, but only MED showed high probability to cross the blood-brain barrier. These results suggest that AT, HAT, and MED are candidates for treating neuropsychiatric disorders, such as depression and cardiovascular disease.</p>
DOI
10.3390/jof7100876
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자연과학대학 > 화학·나노과학전공 > Journal papers
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