Design and Synthesis of Indole-Based Imidazo[1,2- <i>a</i> ]pyridine Derivatives as Antiseizure Candidates: Evaluation in Chemically Induced Seizure Models and <i>In Vitro</i> Antioxidant Assays

Abstract

This study presents the design and synthesis of a targeted series of indole-based derivatives and their assessment as potential antiseizure candidates. The antiseizure activity of the synthesized compounds was evaluated using two chemically induced seizure models, pentylenetetrazole (PTZ) and pilocarpine, to assess their capacity to suppress acute seizure activity in vivo. Several compounds showed dose-specific protection against seizures in both models, supporting acute antiseizure activity under the tested screening conditions. The radical-scavenging properties of the active compounds were evaluated using the DPPH assay as a cell-free chemical measure of radical-quenching capacity. Three lead candidates (9b, 9e, and 9h) were prioritized because they combined favorable dose-specific antiseizure outcomes with DPPH radical-scavenging activity. However, the DPPH findings are interpreted here as evidence of chemical radical-scavenging properties rather than direct proof of a biological antioxidant mechanism underlying the observed antiseizure effects. The findings indicate that the synthesized indole derivatives are promising antiseizure candidates and warrant further preclinical and mechanistic studies, including direct biological evaluation of redox-related pathways in seizure control.