Pharmaceutical Science: New Insights and Developments Vol. 12

Epilepsy is a chronic non-communicable brain disorder that affects about 50 million people worldwide and is characterised by recurrent seizures. Heterocyclic compounds are widely distributed in nature and have diverse applications in the design of new drug molecules, including potential antiepileptic agents. Based on previous findings, selective activation of gamma-aminobutyric acid (GABA)-mediated pathways is an important target for antiepileptic molecule design because GABA helps regulate central nervous system activity. In this study, thiophene derivatives were used to design new antiepileptic agents through selective GABA activation. The probable activity of thiophene derivatives may be improved by substitution at all positions of thiophene except the first position. Molecular docking was performed to predict the antiepileptic activity of the designed analogues. The molecular docking of thiophene analogues was carried out using AutoDock Vina version 1.1.2. Twenty thiophene analogues were docked into GABAa with Protein Data Bank (PDB) code 4COF, and the interaction was assessed based on the docking score. Diazepam was used as the standard compound. The twenty analogues showed docking scores ranging from -6.3 to -9.6 kcal/mol, and thirteen analogues showed more favourable docking scores than diazepam. Compound T-15 showed the lowest docking score and, therefore, higher binding interaction than the other thiophene analogues. All thiophene derivatives showed hydrogen-bond interactions with protein residues. Further synthesis and in vitro evaluation are required to confirm antiepileptic activity.