In Silico Design and Computational Study of Novel 1, 3, 4-Thiadiazole Derivatives as Potential Affinity with NA/H Exchanger Receptor for Anticonvulsant Activity

A series of novel 1, 3, 4-thiadiazole derivatives were designed keeping in view the structural requirement of pharmacophore and Quantitative structure activity relationship (QSAR) and evaluated in silico anticonvulsant activity. Docking procedures allow virtually screening a database of compounds and predict the strongest binder based on various scoring functions. In the docking study, the most active compounds of the series were, VR 2, VR 3 and VR 4 exhibited good binding properties. Result reveals that the protein-ligand interaction energy of derivatives VR 2, VR 3 and VR 4 were -7.08 kcal/mol, -6.64 kcal/mol and -7.42 kcal/mol respectively, which is slightly higher than the standard anticonvulsant phenytoin drug as -6.03 kcal/mol, so that the derivatives have satisfactory affinity with established convulsant receptor namely Na/H exchanger. A computational study was also carried out including prediction of pharmacokinetic properties, toxicity and bioactivity studies. The percentage of absorption (%ABS) was calculatedand observed that all titled compounds exhibited a better %ABS ranging 92.66, 85.81, 90.07 and 86.98, respectively and compared than standard Phenytoin drug as %ABS 88.92. Although VR 1 had slightly lesser protein affinity, its other pharmacological parameters were same like other screened compounds. The above observation suggested that these compounds would serve as better lead compound for anticonvulsant screening for future drug design perspective.