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Potent and selective inhibition of human monoamine oxidase-B by 4-dimethylaminochalcone and selected chalcone derivatives
- Potent and selective inhibition of human monoamine oxidase-B by 4-dimethylaminochalcone and selected chalcone derivatives
- Oh, Jong Min; Kang, Myung-Gyun; Hong, Ahreum; Park, Ji-Eun; Kim, Soo Hyun; Lee, Jae Pil; Baek, Seung Cheol; Park, Daeui; Nam, Sang-Jip; Cho, Myoung-Lae; Kim, Hoon
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
- INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES vol. 137, pp. 426 - 432
- 4-Dimethylaminochalcone; Human monoamine oxidase; Acetylcholinesterase; Dual-targeting function; Docking simulation
- SCIE; SCOPUS
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- Six synthetic (1-6) and six natural (7-12) chalcones were tested for human monoamine oxidases (hMAOs) and acetylcholinesterase (AChE) inhibitory activities. Compounds 4-dimethylaminochalcone (2), 4'-chloro-4-dimethylaminochalcone (5), and 2,4'-dichloro-4-dimethylaminochalcone (1) potently inhibited hMAO-B with IC50 values of 0.029, 0.061, and 0.075 mu M, respectively. 4-Nitrochalcone (4) and 4-chlorochalcone (3) also potently inhibited hMAO-B with IC50 values of 0.066 and 0.082 mu M, respectively (23- and 2.6-fold less than compound 2). Compound 2 had a high selectivity index (113.1) for hMAO-B over hMAO-A (IC50 = 3.28 mu M). Compounds 1 and 2,2'-dihydroxy-4',6'-dimethoxychalcone (12) potently inhibited hMAO-A with IC50 values of 0.18 and 039 mu M, respectively. In addition, compounds 4 and 2 also effectively inhibited AChE with IC50 values of 125 and 6.07 mu M, respectively, and thus, exhibited dual-targeting. Compound 2 reversibly and competitively inhibited hMAO-B with a K-i value of 0.0066 mu M. Docking simulations showed binding affinities of compounds 1 to 5 for hMAO-B were higher than those for hMAO-A or AChE and suggested these five chalcones form hydrogen bonds with MAO-B at Cys172 but that they do not form hydrogen bonds with hMAO-A or AChE. These findings suggest compound 2 be considered a promising and dual-targeting lead compound for the treatment of Alzheimer's disease. (C) 2019 Elsevier B.V. All rights reserved.
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