Murrayanine-hydantoin and -thiohydantoin analogs as promising anti-convulsant agents: synthesis, characterization and molecular docking studies

Based on the fact that three scaffolds; viz.murrayanine, Schiff's base, and hydantoin have been reported to exhibit potent anti-convulsant activity, therefore, all three of them were integrated to shape a hybrid molecule which is believed to demonstrate excellent anti-convulsant activity owing to the incorporation of scaffolds.The present research involved rational designing of anti-convulsant agents having murrayanine scaffold linked with hydantoin moiety via Schiff's base linkage with an objective that the analogs will demonstrate enhanced anti-convulsant activity than their parents and also show comparable activity with the standard drug.The anti-convulsant activity was screened at dose levels of 30, 100, and 300 mg/kg utilizing maximal electroshock-induced seizure (MES) threshold test where molecule (5) displayed the most potent activity at doses 30 mg/kg (0.5 hr) and 100 mg/kg (4 hr), respectively, with comparison to the standard drug, phenytoin.In contrast, the compound (8) compound exhibited activity at 100 mg/kg (0.5 hr) and 300 mg/ kg (4 hr), respectively in male Albino Swiss mice.The research revealed the prospective of murrayanine-Schiff's base-hydantoin derivatives as active anti-convulsant activity.The characterization data were found to be in full agreement with the structural aspects.The molecular docking study revealed the possible interaction of the ligands with the NaVAb voltage-gated sodium channel, thereby proving the possible mechanism of molecule action.This study will certainly promote researchers in the rational synthesis of hybrid molecules with pronounced anti-epileptic activity.