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 (<b>7a</b>-<b>f</b> and <b>11a</b>-<b>c</b>). Several candidates with significant seizure protection were found via initial screening in the PTZ model. In the pilocarpine model, compounds <b>7a</b> and <b>11a</b> 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, <b>11a</b> matched or surpassed valproic acid's effects, especially in lowering astrocytic activation (GFAP), while <b>7a</b> 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 <b>7a</b> and <b>11a</b> in epilepsy therapy by highlighting them as strong, safe, and versatile anticonvulsants.