Antitarget Interaction, Acute Toxicity and Protein Binding Studies of Quinazolinedione Sulphonamides as GABA1 Antagonists

喹唑啉二酮磺酰胺类化合物作为GABA1拮抗剂的抗靶点相互作用、急性毒性和蛋白结合研究

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Abstract

Diseases characterized by recurrent seizures are known as epilepsy. One of the most important mechanisms for handling it is GABA1 receptor mediated inhibition. In the same context while studying the treatment of epilepsy we observed significant effects by derivatives of sulfonamides, which prompted us to design novel derivatives by means of in silico resources with antiepileptic effects. Molecular docking approaches are routinely used in modern drug design to help understand drug-receptor interaction. This study has been performed with the help of Chemdraw Ultra 7.0, GUSAR online tool for IC50 and LD50 predictions, AutoDock Vina (Python Prescription 0.8), and PaDEL software. Results revealed that ligand-protein interaction affinity of all 10 designed molecules ranges from -5.7 Kcal/mol to -5.2 Kcal/mol, which is approximately comparable to pre-existing GABA1 inhibitor i.e. phenytoin (CID: 1775, ligand-protein interaction affinity is -6.5 Kcal/mol).

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