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

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.