Identification of Novel Triazole-Pyrazole Conjugates as Potential Anticonvulsant Agents: Synthesis and Biological Evaluations.

Abstract

Since epilepsy is still a complex neurological condition, better and more efficient treatment methods are needed. This study used PTZ- and PIL-induced seizure models to evaluate the anticonvulsant activity of some recently synthesized compounds (7a-f and 11a-c). Several candidates with significant seizure protection were found via initial screening in the PTZ model. In the pilocarpine model, compounds 7a and 11a showed the most promising efficacy by considerably delaying the start of seizures, lowering their severity, and increasing survival. According to biochemical analysis, both compounds successfully reduced oxidative stress, neuroinflammation, glial activation, and hippocampal excitotoxicity. Notably, 11a matched or surpassed valproic acid's effects, especially in lowering astrocytic activation (GFAP), while 7a performed better across all assessed parameters. The toxicological assessments validated both compounds' safety, and no evidence of neurotoxic, hepatic, renal, or cardiac damage was found. These results indicate the potential for additional preclinical development of 7a and 11a in epilepsy therapy by highlighting them as strong, safe, and versatile anticonvulsants.