期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 151, 期 -, 页码 441-448出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2020.02.144
关键词
Maackia amurensis; Calycosin; 8-O-Methylretusin; Selective human monoamine oxidase-B inhibitor; Docking simulation
资金
- Basic Science Research Program through the National Research Foundation (NRF) of Korea - Ministry of Education [2017R1D1A3B03028559]
- KRIBB Research Initiative Program - Ministry of Science and ICT (MSIT) of Republic of Korea
- R&D Program for Forest Science Technology, Korea Forest Service (Korea Forestry Promotion Institute) [2017030A00-1919-BA01]
- National Research Foundation of Korea [2017R1D1A3B03028559] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Nineteen compounds were isolated from the stems of Maackia amurensis by activity-guided screening for new human monoamine oxidase-B (hMAO-B) inhibitors. Among the compounds isolated, flavonoids calycosin (5) and 8-O-methylretusin (6) were found to potently and selectively inhibit hMAO-B (IC50 = 0.24 and 0.23 mu M,respectively) but not hMAO-A with high selectivity index (SI) values (SI = 293.8 and 81.3, respectively). In addition, 5 and 6 reversibly and competitively inhibited hMAO-B with K-i values of 0.057 and 0.054 mu M. respectively. A pterocarpan (-)-medicarpin (18) was also observed to strongly inhibit hMAO-B (IC50 030 mu M). Most of the compounds weakly inhibited AChE, except isolupalbigenin (13) (IC50 = 20.6 mu M), which suggested 13 be considered a potential dual function inhibitor of MAO-B and AChE. Molecular docking simulation revealed that the binding affinities of 5 and 6 for hMAO-B (both -9.3 kcal/mol) were higher than those for hMAO-A (-7.4 and -7.2 kcal/mol, respectively). Compound 5 was found to interact by hydrogen bonding with hMAO-B at Cys172 residue (distance: 3.250 A); no hydrogen bonding was predicted between 5 and hMAO-angstrom. These findings suggest that compounds 5 and 6 be considered novel potent, selective, and reversible hMAO-B inhibitors and candidates for the treatment of neurological disorders. (C) 2020 Elsevier B.V. All rights reserved.
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