Potent and selective inhibition of human monoamine oxidase-B by 4-dimethylaminochalcone and selected chalcone derivatives
- 주제(키워드) 4-Dimethylaminochalcone , Acetylcholinesterase , Docking simulation , Dual-targeting function , Human monoamine oxidase
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier B.V.
- 발행년도 2019
- URI http://www.dcollection.net/handler/ewha/000000160777
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.ijbiomac.2019.06.167
- PubMed https://pubmed.ncbi.nlm.nih.gov/31271801
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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 μM, respectively. 4-Nitrochalcone (4) and 4-chlorochalcone (3) also potently inhibited hMAO-B with IC50 values of 0.066 and 0.082 μM, respectively (2.3- 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 μM). Compounds 1 and 2,2′-dihydroxy-4′,6′-dimethoxychalcone (12) potently inhibited hMAO-A with IC50 values of 0.18 and 0.39 μM, respectively. In addition, compounds 4 and 2 also effectively inhibited AChE with IC50 values of 1.25 and 6.07 μM, respectively, and thus, exhibited dual-targeting. Compound 2 reversibly and competitively inhibited hMAO-B with a Ki value of 0.0066 μM. 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. © 2019 Elsevier B.V.
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