2. Academic Validation
  3. Design, synthesis and evaluation of quinoline- O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease

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

  • J Enzyme Inhib Med Chem. 2023 Dec;38(1):2169682. doi: 10.1080/14756366.2023.2169682.
Hongsong Chen 1,  Jing Mi 2,  Sen Li 3,  Zhengwei Liu 2,  Jing Yang 2,  Rui Chen 4,  Yujie Wang 4,  Yujuan Ban 4,  Yi Zhou 2,  Wu Dong 1,  Zhipei Sang 2 5
Affiliations

Affiliations

  • 1 Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicology, College of Animal Science and Technology, Inner Mongolia Minzu University, Tongliao, Inner Mongolia, China.
  • 2 College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang, Henan, China.
  • 3 Department of Orthopaedics Surgery, Nanyang Central Hospital, Nanyang, Henan, China.
  • 4 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.
  • 5 School of Pharmaceutical Sciences, Hainan University, Haikou, Hainan, China.
PMID: 36688444 DOI: 10.1080/14756366.2023.2169682
Abstract

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.

Keywords

Alzheimer’s disease; multifunctional agent; quinoline-O-carbamate derivatives; zebrafish AD model.

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