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Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors.
Bioorg Med Chem. 2014 Nov 01; 22(21):6124-33.BM

Abstract

A novel series of chalcone derivatives (4a-8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The logP values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 μmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 μmol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE.

Authors+Show Affiliations

College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China. Electronic address: pharmaliu@126.com.College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.College of Pharmacy, Hu'nan University of Traditional Chinese Medicine (TCM), Changsha 410208, China.College of Chemistry and Chemical Engineering, Hu'nan University, Changsha 410082, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25260958

Citation

Liu, Hao-ran, et al. "Design, Synthesis and Pharmacological Evaluation of Chalcone Derivatives as Acetylcholinesterase Inhibitors." Bioorganic & Medicinal Chemistry, vol. 22, no. 21, 2014, pp. 6124-33.
Liu HR, Liu XJ, Fan HQ, et al. Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors. Bioorg Med Chem. 2014;22(21):6124-33.
Liu, H. R., Liu, X. J., Fan, H. Q., Tang, J. J., Gao, X. H., & Liu, W. K. (2014). Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors. Bioorganic & Medicinal Chemistry, 22(21), 6124-33. https://doi.org/10.1016/j.bmc.2014.08.033
Liu HR, et al. Design, Synthesis and Pharmacological Evaluation of Chalcone Derivatives as Acetylcholinesterase Inhibitors. Bioorg Med Chem. 2014 Nov 1;22(21):6124-33. PubMed PMID: 25260958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors. AU - Liu,Hao-ran, AU - Liu,Xian-jun, AU - Fan,Hao-qun, AU - Tang,Jing-jing, AU - Gao,Xiao-hui, AU - Liu,Wu-Kun, Y1 - 2014/09/04/ PY - 2014/07/09/received PY - 2014/08/22/revised PY - 2014/08/26/accepted PY - 2014/9/28/entrez PY - 2014/9/28/pubmed PY - 2015/7/17/medline KW - AChE inhibitors KW - Chalcone derivatives KW - LogP KW - Molecular docking SP - 6124 EP - 33 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 22 IS - 21 N2 - A novel series of chalcone derivatives (4a-8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The logP values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 μmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 μmol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/25260958/Design_synthesis_and_pharmacological_evaluation_of_chalcone_derivatives_as_acetylcholinesterase_inhibitors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(14)00628-2 DB - PRIME DP - Unbound Medicine ER -