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Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation.
Bioorg Chem. 2019 03; 84:137-149.BC

Abstract

A series of salicylamide 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. They showed good inhibitory activities of self- and Cu2+-induced Aβ1-42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward RatAChE and EeAChE with IC50 value of 10.4 μM and 15.2 μM, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency (42.5% and 31.4% at 25.0 μM, respectively) and moderate disaggregation ability to self- and Cu2+-induced Aβ1-42 aggregation fibrils (23.4% and 27.0% at 25 μM, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment.

Authors+Show Affiliations

Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.Institute of Traditional Chinese Medicine Pharmacology and Toxicology, Sichuan Academy of Chinese Medicine Sciences, Chengdu 610041, PR China.Department of Medicinal Chemistry, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China. Electronic address: dengyong@scu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

30500523

Citation

Song, Qing, et al. "Novel Salicylamide Derivatives as Potent Multifunctional Agents for the Treatment of Alzheimer's Disease: Design, Synthesis and Biological Evaluation." Bioorganic Chemistry, vol. 84, 2019, pp. 137-149.
Song Q, Li Y, Cao Z, et al. Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation. Bioorg Chem. 2019;84:137-149.
Song, Q., Li, Y., Cao, Z., Qiang, X., Tan, Z., & Deng, Y. (2019). Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation. Bioorganic Chemistry, 84, 137-149. https://doi.org/10.1016/j.bioorg.2018.11.022
Song Q, et al. Novel Salicylamide Derivatives as Potent Multifunctional Agents for the Treatment of Alzheimer's Disease: Design, Synthesis and Biological Evaluation. Bioorg Chem. 2019;84:137-149. PubMed PMID: 30500523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel salicylamide derivatives as potent multifunctional agents for the treatment of Alzheimer's disease: Design, synthesis and biological evaluation. AU - Song,Qing, AU - Li,Yan, AU - Cao,Zhongcheng, AU - Qiang,Xiaoming, AU - Tan,Zhenghuai, AU - Deng,Yong, Y1 - 2018/11/22/ PY - 2018/10/07/received PY - 2018/11/14/revised PY - 2018/11/17/accepted PY - 2018/12/1/pubmed PY - 2020/1/16/medline PY - 2018/12/1/entrez KW - Acetylcholinesterase inhibitors KW - Alzheimer’s disease KW - Anti-neuroinflammatory agents KW - Antioxidant KW - Aβ aggregation inhibitors KW - Salicylamide derivatives SP - 137 EP - 149 JF - Bioorganic chemistry JO - Bioorg Chem VL - 84 N2 - A series of salicylamide 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. They showed good inhibitory activities of self- and Cu2+-induced Aβ1-42 aggregation, and significant antioxidant activities. Among them, compound 15b exhibited good inhibitory activity toward RatAChE and EeAChE with IC50 value of 10.4 μM and 15.2 μM, respectively. Moreover, 15b displayed high antioxidant activity (2.46 Trolox equivalents), good self- and Cu2+-induced Aβ1-42 aggregation inhibitory potency (42.5% and 31.4% at 25.0 μM, respectively) and moderate disaggregation ability to self- and Cu2+-induced Aβ1-42 aggregation fibrils (23.4% and 27.0% at 25 μM, respectively). Furthermore, 15b also showed biometal chelating abilities, anti-neuroinflammatory ability and BBB permeability. These multifunctional properties indicated compound 15b was worthy of being chosen for further pharmacokinetics, toxicity and behavioral researches to test its potential for AD treatment. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/30500523/Novel_salicylamide_derivatives_as_potent_multifunctional_agents_for_the_treatment_of_Alzheimer's_disease:_Design_synthesis_and_biological_evaluation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(18)31141-6 DB - PRIME DP - Unbound Medicine ER -