Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer’s disease

Hongsong Chen; Jing Mi; Sen Li; Zhengwei Liu; Jing Yang; Rui Chen; Yujie Wang; Yujuan Ban; Yi Zhou; Wu Dong; Zhipei Sang

doi:10.1080/14756366.2023.2169682

Journal of Enzyme Inhibition and Medicinal Chemistry (Dec 2023)

Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer’s disease

Hongsong Chen,
Jing Mi,
Sen Li,
Zhengwei Liu,
Jing Yang,
Rui Chen,
Yujie Wang,
Yujuan Ban,
Yi Zhou,
Wu Dong,
Zhipei Sang

Affiliations

Hongsong Chen: Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
Jing Mi: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China
Sen Li: Department of Orthopaedics Surgery, Nanyang Central Hospital, Nanyang, Henan, China
Zhengwei Liu: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China
Jing Yang: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China
Rui Chen: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, China
Yujie Wang: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, China
Yujuan Ban: State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, Guizhou, China
Yi Zhou: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China
Wu Dong: Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China
Zhipei Sang: College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China

DOI: https://doi.org/10.1080/14756366.2023.2169682
Journal volume & issue: Vol. 38, no. 1

Abstract

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A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer’s disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The in vitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC50 values of 1.3 µM and 0.81 µM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1β and NO. In addition, compound 3f presented significant neuroprotective effect on Aβ25-35-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes in vitro and plasma. Furthermore, compound 3f could improve AlCl3-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.

Published in Journal of Enzyme Inhibition and Medicinal Chemistry

ISSN: 1475-6366 (Print); 1475-6374 (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.tandfonline.com/journals/ienz

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Abstract

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