Design, Green Synthesis of Piperlongumine Analogs and Their Antioxidant Activity against Cerebral Ischemia-reperfusion Injury

The supplementation of exogenous antioxidants to scavenge excessive reactive oxygen species (ROS) is an effective treatment for cerebral ischemia reperfusion injury (CIRI). Piperlongumine (PL) is a kind of natural product which has a great potential as neuroprotective agents, but it also has obvious neurotoxicity. Moreover, its neuroprotective effects remain to be improved. In this study, a series of novel PL analogs were designed on the foundation of the screened low-toxic diketene skeleton with antioxidation and the 3,4,5-trimethoxyphenyl group, which maybe increase the antioxidant activity of PL. The cytotoxicity and activity tests on a series of PL analogs which were synthesized by a novel green synthesis method indicated that all of these compounds without obvious toxicity have remarkable antioxidant effects, especially compared with diketene skeletons and PL. The cytoprotection of the active compound also decreased significantly when the carbon-carbon double bonds of the molecular skeleton were redu...