Synthesis and evolution of neuroprotective effects of oxymatrine derivatives as anti‐Alzheimer’s disease agents

While screening for natural product scaffolds as potential anti‐Alzheimer's disease (AD), oxymatrine (OMT) was found to relieve symptoms of AD through diminishing death of neuronal cells caused by microglia‐induced inflammation. In this study, 13 derivatives of OMT were synthesized and their neuroprotective effects were evaluated on Aβ1‐42‐induced PC12 cells using MTT method. In addition, the best neuroprotective potencies were obtained with compounds 4, 6e, and 6f, which were selected for evaluation of decrease in IL‐1β and TNF‐α in Aβ1‐42‐treated PC12 cells. Collectively, these data reveal that derivatives 6e and 6f possess the best ability of diminish IL‐1β production and reverse cell damage in all compounds, which are possible to develop as therapeutic agents for AD. A series of 13 OMT derivatives were synthesis, and their neuroprotective effects were evaluated. Two derivatives possess better neuroprotective effects than OMT, which was proven have strong anti‐AD effects in mice.