Synthesis and in silico and in vivo anticonvulsant activities of substituted 2-phenyl indole derivatives

In this study, a series of indole-based derivatives (2a to 2f) were synthesized, followed by a main base reaction from the starting material, phenylhydrazine, and substituted acetophenone in glacial acetic acid, and all the synthesized structures were characterized by IR, NMR, and mass spectrometry. The anticonvulsant activities of the synthesized derivatives were subsequently screened using a maximal electroshock model. Compounds 2b, 2c and 2e exhibited moderate activity against the extensor seizure phase compared with the standard drug phenytoin sodium. To determine the mechanism of action of the synthesized compounds, a docking study was performed against gamma-butyric acid (a GABAA receptor), and the AMPA-sensitive glutamate receptor was shown to have good binding interactions. 2b, 2c, and 2c exhibited good binding energies for AMPA. Among the six synthesized compounds, 2b, 2c, and 2e were found to possess optimum to excellent in silico ADME properties. Substituted 2-phenylindole derivatives also increase the therapeutic value of 2-phenylindole cores for the discovery of potent anticonvulsive agents. Thus, we observed that 2-phenylindole in combination with other heterocycles might be used as a lead compound for further study and for developing such compounds as suitable lead molecules with improved pharmacological profiles.