Abstract
In this study, a series of indole-based derivatives (2a-f) was synthesized, followed by a Mannich base reaction from the starting materials, substituted phenylhydrazine and substituted acetophenone, in glacial acetic acid. All the synthesized derivatives were characterized by IR, NMR, Mass and screened for anticonvulsant activity using the maximal electroshock model. Among all, 2b, 2c and 2e exhibited potent anticonvulsant activity as compared to standard drug phenytoin sodium. In our study, we carried out an in-silico study against GABA receptor, and the AMPA-sensitive glutamate. Docking study revealed that 2b, 2c, 2e showed good binding energy against AMPA receptor. Among the six synthesized compounds 2b, 2c, and 2e were found to possess an optimum to excellent in- silico ADME properties. Our results showed that substituting a 2-phenylindole derivative also increases the therapeutic value of the 2-phenylindole core, which is needed for the discovery of a potent anticonvulsant agent. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-025-00517-z.