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Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease.
Eur J Med Chem. 2017 Jan 27; 126:762-775.EJ

Abstract

A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50 = 0.00878 ± 0.0002 μM, 0.0212 ± 0.006 μM and 0.0371 ± 0.004 μM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD.

Authors+Show Affiliations

Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu, 610041, China.Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu, 610041, China.Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan academy of Chinese Medicine Sciences, Chengdu, 610041, China. Electronic address: tanzhh616@163.com.Department of Medicinal Chemistry, Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China. Electronic address: dengyong@scu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27951485

Citation

Li, Yan, et al. "Aurone Mannich Base Derivatives as Promising Multifunctional Agents With Acetylcholinesterase Inhibition, Anti-β-amyloid Aggragation and Neuroprotective Properties for the Treatment of Alzheimer's Disease." European Journal of Medicinal Chemistry, vol. 126, 2017, pp. 762-775.
Li Y, Qiang X, Luo L, et al. Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease. Eur J Med Chem. 2017;126:762-775.
Li, Y., Qiang, X., Luo, L., Yang, X., Xiao, G., Liu, Q., Ai, J., Tan, Z., & Deng, Y. (2017). Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease. European Journal of Medicinal Chemistry, 126, 762-775. https://doi.org/10.1016/j.ejmech.2016.12.009
Li Y, et al. Aurone Mannich Base Derivatives as Promising Multifunctional Agents With Acetylcholinesterase Inhibition, Anti-β-amyloid Aggragation and Neuroprotective Properties for the Treatment of Alzheimer's Disease. Eur J Med Chem. 2017 Jan 27;126:762-775. PubMed PMID: 27951485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease. AU - Li,Yan, AU - Qiang,Xiaoming, AU - Luo,Li, AU - Yang,Xia, AU - Xiao,Ganyuan, AU - Liu,Qi, AU - Ai,Jiachen, AU - Tan,Zhenghuai, AU - Deng,Yong, Y1 - 2016/12/05/ PY - 2016/10/06/received PY - 2016/11/28/revised PY - 2016/12/03/accepted PY - 2016/12/13/pubmed PY - 2017/2/22/medline PY - 2016/12/13/entrez KW - Acetylcholinesterase inhibitors KW - Alzheimer's disease KW - Aurone Mannich base derivatives KW - Aβ aggregation inhibitors KW - Multifunctional agents SP - 762 EP - 775 JF - European journal of medicinal chemistry JO - Eur J Med Chem VL - 126 N2 - A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50 = 0.00878 ± 0.0002 μM, 0.0212 ± 0.006 μM and 0.0371 ± 0.004 μM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD. SN - 1768-3254 UR - https://www.unboundmedicine.com/medline/citation/27951485/Aurone_Mannich_base_derivatives_as_promising_multifunctional_agents_with_acetylcholinesterase_inhibition_anti_β_amyloid_aggragation_and_neuroprotective_properties_for_the_treatment_of_Alzheimer's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0223-5234(16)31015-7 DB - PRIME DP - Unbound Medicine ER -