| Title : Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease - Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682 |
| Author(s) : Chen H , Mi J , Li S , Liu Z , Yang J , Chen R , Wang Y , Ban Y , Zhou Y , Dong W , Sang Z |
| Ref : J Enzyme Inhib Med Chem , 38 :2169682 , 2023 |
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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 IC(50) values of 1.3 microM and 0.81 microM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1beta and NO. In addition, compound 3f presented significant neuroprotective effect on Abeta(25-35)-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 AlCl(3)-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD. |
| PubMedSearch : Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682 |
| PubMedID: 36688444 |
Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y, Dong W, Sang Z (2023)
Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease
J Enzyme Inhib Med Chem
38 :2169682
Chen H, Mi J, Li S, Liu Z, Yang J, Chen R, Wang Y, Ban Y, Zhou Y, Dong W, Sang Z (2023)
J Enzyme Inhib Med Chem
38 :2169682