Design, Synthesis, and Biological Evaluation of Novel Tetramethylpyrazine- nitrone Derivatives as Antioxidants

Background: Thrombolysis and endovascular thrombectomy are the two main therapeutic strategies for ischemic stroke in clinic. However, reperfusion injury causes oxidative stress leading to overproduction of reactive oxygen species, mitochondrial dysfunction and subsequent cell death. Methods: We designed and synthesized two tetramethylpyrazine-nitrone derivatives (T-003 and T- 005) and investigated their abilities for scavenging free radicals and protective effects as well as neurite outgrowth promotion in vitro. Results: Both of them showed potent radical-scavenging activity and neuroprotective effects against iodoacetic acid-induced cell injury. Furthermore, T-003 and T-005 significantly promoted neurite outgrowth in PC12 cells. Conclusion: Our results suggest that compound T-003 and T-005 could be potent antioxidants for the treatment of neurological disease, particularly ischemic stroke.