Discovery of 1,2,4-triazole derivatives as novel neuroprotectants against cerebral ischemic injury by activating antioxidant response element

Bioorg Chem. 2022 Aug 13;128:106096. doi: 10.1016/j.bioorg.2022.106096. Online ahead of print.ABSTRACTAcute ischemic stroke is an important cause of death and long-term disability worldwide. In this work, we have synthesized a series of derivatives with 3,5‑diaryl substituent triazole scaffolds. The derivatives showed favorable protective effective in SNP-induced oxidative stress model, of which compound 5 was the most active. In vivo experiments showed that compound 5 could ameliorate neurological deficits, attenuate infarction sizes, reduce malonaldehyde (MDA) level and increase superoxide dismutase (SOD) level in middle cerebral artery occlusion (MCAO) rats. Preliminary safety evaluation showed that compound 5 exhibited low acute toxicity in BALB/c mice (LD50 greater than 1000 mg/kg). Further investigation indicated that compound 5 was able to scavenge ROS, restore mitochondrial membrane potential and protect PC12 cells from SNP-induced apoptosis. Moreover, compound 5 could initiate transcription of antioxidant response element (ARE) and induced expressions of antioxidative enzymes. Collectively, compound 5 might have the potency of treating acute ischemic stroke.PMID:35985158 | DOI:10.1016/j.bioorg.2022.106096
Source: Bioorganic Chemistry - Category: Chemistry Authors: Source Type: research