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Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment.
Bioorg Chem. 2018 08; 78:298-306.BC

Abstract

A series of pterostilbene β-amino alcohol derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro assays demonstrated that most of the derivatives were selective acetylacholinesterase (AChE) inhibitors with moderate multifunctional properties. Among them, compound 5f exhibited the best inhibitory activity for EeAChE (IC50 = 24.04 μM), that was better than pterostilbene under our experimental condition. In addition, compound 5f displayed reasonable antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. Moreover, 5f also showed self-induced Aβ1-42 aggregation inhibitory potency and displayed high BBB permeability in vitro. These multifunctional properties highlight 5f as a 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.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. 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29625269

Citation

Zheng, Yunxiaozhu, et al. "Design, Synthesis and Evaluation of Pterostilbene Β-amino Alcohol Derivatives as Multifunctional Agents for Alzheimer's Disease Treatment." Bioorganic Chemistry, vol. 78, 2018, pp. 298-306.
Zheng Y, Qiang X, Xu R, et al. Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment. Bioorg Chem. 2018;78:298-306.
Zheng, Y., Qiang, X., Xu, R., Song, Q., Tian, C., Liu, H., Li, W., Tan, Z., & Deng, Y. (2018). Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment. Bioorganic Chemistry, 78, 298-306. https://doi.org/10.1016/j.bioorg.2018.03.016
Zheng Y, et al. Design, Synthesis and Evaluation of Pterostilbene Β-amino Alcohol Derivatives as Multifunctional Agents for Alzheimer's Disease Treatment. Bioorg Chem. 2018;78:298-306. PubMed PMID: 29625269.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis and evaluation of pterostilbene β-amino alcohol derivatives as multifunctional agents for Alzheimer's disease treatment. AU - Zheng,Yunxiaozhu, AU - Qiang,Xiaoming, AU - Xu,Rui, AU - Song,Qing, AU - Tian,Chaoquan, AU - Liu,Hongyan, AU - Li,Wei, AU - Tan,Zhenghuai, AU - Deng,Yong, Y1 - 2018/03/28/ PY - 2018/01/12/received PY - 2018/03/13/revised PY - 2018/03/18/accepted PY - 2018/4/7/pubmed PY - 2019/1/29/medline PY - 2018/4/7/entrez KW - Acetylcholinesterase inhibitors KW - Alzheimer’s disease KW - Aβ aggregation inhibitors KW - Multifunctional agents KW - Neuroprotective effects KW - Pterostilbene β-amino alcohol derivatives SP - 298 EP - 306 JF - Bioorganic chemistry JO - Bioorg Chem VL - 78 N2 - A series of pterostilbene β-amino alcohol derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro assays demonstrated that most of the derivatives were selective acetylacholinesterase (AChE) inhibitors with moderate multifunctional properties. Among them, compound 5f exhibited the best inhibitory activity for EeAChE (IC50 = 24.04 μM), that was better than pterostilbene under our experimental condition. In addition, compound 5f displayed reasonable antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. Moreover, 5f also showed self-induced Aβ1-42 aggregation inhibitory potency and displayed high BBB permeability in vitro. These multifunctional properties highlight 5f as a promising candidate for further studies directed to the development of novel drugs against AD. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/29625269/Design_synthesis_and_evaluation_of_pterostilbene_β_amino_alcohol_derivatives_as_multifunctional_agents_for_Alzheimer's_disease_treatment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(18)30031-2 DB - PRIME DP - Unbound Medicine ER -