Design, synthesis and neuroprotective activities of novel cinnamide derivatives containing benzylpiperazine moiety

AbstractA new series of cinnamide derivatives6a–l were synthesized by the reaction of acyl chlorides with various substituted benzylpiperazines. The structures were characterized by1H NMR,13C NMR, and HRMS. The potential neuroprotective activities of cinnamide analogs were evaluated in differentiated rat pheochromocytoma cells (PC12 cells) and in mice subjected to acute cerebral ischemia. Among the series,6a,6b, and6c, featuring a 1,3-benzodioxole moiety, showed potent neuroprotection both in vivo and in vitro. The three compounds were selected and further studied to determine their mechanism of action. MTT assay, Hoechst 33342/PI double staining, and high content screening (HCS) revealed that pretreatment of the cells with6a,6b, and6c has significantly decreased the extent of cell apoptosis in a dose-dependent manner. The results of western blot analysis demonstrated these compounds suppressed apoptosis of glutamate-induced PC12 cells via caspase-3 pathway. These compounds can be lead compounds for further discovery of neuroprotective agents for treating cerebral ischemic stroke.

Source: Medicinal Chemistry Research - February 22, 2018 Category: Chemistry Source Type: research