Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents

Publication date: Available online 7 January 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Jiabing Wang, Lili Huang, Chanchan Cheng, Ge Li, Jingwen Xie, Mengya Shen, Qian Chen, Wulan Li, Wenfei He, Peihong Qiu, Jianzhang WuAbstractScavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred potent protection of H2O2-induced oxidative damage in the neuron-like PC12 cells, but also played a neuroprotective role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.Graphical abstractChalcone analogue 33 conferred protection of PC12 cells against H2O2 insult with novel dual-antioxidant mechanism of directly scave...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research