biostudies-literatureUnknown15Pang SAlzheimer's disease (AD) is a neurodegenerative disease characterized by progressive neurodegeneration and cognitive decline. Evodiamine, a main component in Chinese medicine, was found to improve cognitive impairment in AD model mice based on several intensive studies. However, evodiamine has high cytotoxicity and poor bioactivity. In this study, several evodiamine derivatives were synthesized <i>via</i> heterocyclic substitution and amide introduction and screened for cytotoxicity and antioxidant capacity. Under the same concentrations, compound <b>4c</b> was found to exhibit lower cytotoxicity and higher activity against H₂O₂ and amyloid β oligomers (AβOs) than evodiamine <i>in vitro</i> and significantly improve the working memory and spatial memory of 3 x Tg and Frontiers in molecular neuroscience1025066https://www.ebi.ac.uk/biostudies/studies/S-EPMC9868638biostudies-literatureDiscovery of an evodiamine derivative for PI3K/AKT/GSK3β pathway activation and AD pathology improvement in mouse models.PMC9868638Dong WLuo ZPan SLiu NGuan FZhang LPang SYang YLi SQi XZhang XGao XCheng HGao SfalseDiscovery of an evodiamine derivative for PI3K/AKT/GSK3β pathway activation and AD pathology improvement in mouse models.Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive neurodegeneration and cognitive decline. Evodiamine, a main component in Chinese medicine, was found to improve cognitive impairment in AD model mice based on several intensive studies. However, evodiamine has high cytotoxicity and poor bioactivity. In this study, several evodiamine derivatives were synthesized <i>via</i> heterocyclic substitution and amide introduction and screened for cytotoxicity and antioxidant capacity. Under the same concentrations, compound <b>4c</b> was found to exhibit lower cytotoxicity and higher activity against H₂O₂ and amyloid β oligomers (AβOs) than evodiamine <i>in vitro</i> and significantly improve the working memory and spatial memory of 3 x Tg and 2022-01-01T00:00:00Z20222026-05-28T06:08:16.344Z2025-04-04T03:42:20.766ZS-EPMC98686383669878010.3389/fnmol.2022.1025066