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Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease.
Bioorg Med Chem Lett. 2013 May 01; 23(9):2636-41.BM

Abstract

A new series of flavonoid derivatives were designed, synthesized and evaluated as potential multifunctional AChE inhibitors against Alzheimer's disease. Most of them exhibited potent AChE inhibitory activity, high selectivity for AChE over BuChE, and moderate to good inhibitory potency toward Aβ aggregation. Specifically, compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofold more potent than tacrine, and it also had ability to inhibit Aβ aggregation (close to the reference compound) and to function as a metal chelator. Molecular modeling and enzyme kinetic study revealed that it targeted both the catalytic active site and the peripheral anionic site of AChE. Consequently, this class of compounds deserved to be thoroughly and systematically studied for the treatment of Alzheimer's disease.

Authors+Show Affiliations

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23511019

Citation

Li, Ren-Shi, et al. "Design, Synthesis and Evaluation of Flavonoid Derivatives as Potential Multifunctional Acetylcholinesterase Inhibitors Against Alzheimer's Disease." Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 9, 2013, pp. 2636-41.
Li RS, Wang XB, Hu XJ, et al. Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease. Bioorg Med Chem Lett. 2013;23(9):2636-41.
Li, R. S., Wang, X. B., Hu, X. J., & Kong, L. Y. (2013). Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease. Bioorganic & Medicinal Chemistry Letters, 23(9), 2636-41. https://doi.org/10.1016/j.bmcl.2013.02.095
Li RS, et al. Design, Synthesis and Evaluation of Flavonoid Derivatives as Potential Multifunctional Acetylcholinesterase Inhibitors Against Alzheimer's Disease. Bioorg Med Chem Lett. 2013 May 1;23(9):2636-41. PubMed PMID: 23511019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer's disease. AU - Li,Ren-Shi, AU - Wang,Xiao-Bing, AU - Hu,Xiao-Jun, AU - Kong,Ling-Yi, Y1 - 2013/03/01/ PY - 2012/12/21/received PY - 2013/02/09/revised PY - 2013/02/21/accepted PY - 2013/3/21/entrez PY - 2013/3/21/pubmed PY - 2013/11/10/medline SP - 2636 EP - 41 JF - Bioorganic & medicinal chemistry letters JO - Bioorg Med Chem Lett VL - 23 IS - 9 N2 - A new series of flavonoid derivatives were designed, synthesized and evaluated as potential multifunctional AChE inhibitors against Alzheimer's disease. Most of them exhibited potent AChE inhibitory activity, high selectivity for AChE over BuChE, and moderate to good inhibitory potency toward Aβ aggregation. Specifically, compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofold more potent than tacrine, and it also had ability to inhibit Aβ aggregation (close to the reference compound) and to function as a metal chelator. Molecular modeling and enzyme kinetic study revealed that it targeted both the catalytic active site and the peripheral anionic site of AChE. Consequently, this class of compounds deserved to be thoroughly and systematically studied for the treatment of Alzheimer's disease. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/23511019/Design_synthesis_and_evaluation_of_flavonoid_derivatives_as_potential_multifunctional_acetylcholinesterase_inhibitors_against_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(13)00282-5 DB - PRIME DP - Unbound Medicine ER -