IDENTIFICATION OF NOVEL IMIDAZOLE DERIVATIVES WITH PROMISING ANTIEPILEPTIC AND ANTIDEPRESSANT ACTIVITIES: NEUROPHARMACOLOGICAL AND IN SILICO STUDIES
Imidazole scaffolds are well-established pharmacophores in widely used anticonvulsant and antidepressant medications, including Dizimol, Nafimidone, and Napamezole hydrochloride. In the present study, two imidazolederivatives (C1 and C3) were synthesised via a green chemistry route using diketones and substituted aldehydes andwere evaluated for neuropharmacological activity. Molecular docking was performed against the Gamma- aminobutyric acid receptor (PDB ID: 8G4N), sodium channel inactivator (PDB ID: 5VB8), and the monoaminetransporter complex (PDB ID: 2QJU) to elucidate their potential mechanisms of action. Compound C1 exhibitedastronger affinity toward the sodium channel (–9.4 kcal/mol), while C3 showed comparable binding across all targets. Free radical scavenging activity, assessed using the 2,2-diphenyl-1-picrylhydrazyl assay, revealed superior antioxidant potential for C3, with a radical scavenging activity of 84.15%. Neuropharmacological activities wereevaluated in Swiss albino mice using an Actophotometer, rotarod, and pentylenetetrazol-induced seizure model at doses of 50 and 100 mg/kg. Both C1 and C3 produced significant Central Nervous System depressant and musclerelaxant effects, with C1 showing greater protection against Pentylenetetrazol induced seizures at a dose of 100mg/kg. Overall, these results suggest that C1 and C3 possess dose-dependent anticonvulsant, antidepressant, andneuroprotective properties, which supports SDG-3. These derivatives can be potential lead candidates for multifunctional neuroactive drug development in the future.
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