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Design, synthesis, and biological evaluation of scutellarein carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease.
Chem Biol Drug Des. 2015 Nov; 86(5):1168-77.CB

Abstract

A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 ± 0.03 μm and 22.1 ± 0.15 μm, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step-down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent 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 Pharmacology, Fourth Military Medical University, Xi'an, 710032, 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.

Pub Type(s)

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

Language

eng

PubMed ID

25941042

Citation

Sang, Zhi-Pei, et al. "Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease." Chemical Biology & Drug Design, vol. 86, no. 5, 2015, pp. 1168-77.
Sang ZP, Qiang XM, Li Y, et al. Design, synthesis, and biological evaluation of scutellarein carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease. Chem Biol Drug Des. 2015;86(5):1168-77.
Sang, Z. P., Qiang, X. M., Li, Y., Wu, B., Zhang, H., Zhao, M. G., & Deng, Y. (2015). Design, synthesis, and biological evaluation of scutellarein carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease. Chemical Biology & Drug Design, 86(5), 1168-77. https://doi.org/10.1111/cbdd.12580
Sang ZP, et al. Design, Synthesis, and Biological Evaluation of Scutellarein Carbamate Derivatives as Potential Multifunctional Agents for the Treatment of Alzheimer's Disease. Chem Biol Drug Des. 2015;86(5):1168-77. PubMed PMID: 25941042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Design, synthesis, and biological evaluation of scutellarein carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease. AU - Sang,Zhi-Pei, AU - Qiang,Xiao-Ming, AU - Li,Yan, AU - Wu,Bei, AU - Zhang,Hui, AU - Zhao,Ming-Gao, AU - Deng,Yong, Y1 - 2015/05/20/ PY - 2014/12/08/received PY - 2015/03/15/revised PY - 2015/04/28/accepted PY - 2015/5/6/entrez PY - 2015/5/6/pubmed PY - 2016/8/2/medline KW - AChE inhibitors KW - Alzheimer's disease KW - antioxidant KW - metal chelator KW - neuroprotective effects KW - scutellarein carbamates KW - synthesis SP - 1168 EP - 77 JF - Chemical biology & drug design JO - Chem Biol Drug Des VL - 86 IS - 5 N2 - A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 ± 0.03 μm and 22.1 ± 0.15 μm, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step-down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD. SN - 1747-0285 UR - https://www.unboundmedicine.com/medline/citation/25941042/Design_synthesis_and_biological_evaluation_of_scutellarein_carbamate_derivatives_as_potential_multifunctional_agents_for_the_treatment_of_Alzheimer's_disease_ L2 - https://doi.org/10.1111/cbdd.12580 DB - PRIME DP - Unbound Medicine ER -