Design and Evaluation of Thiophene Incorporated Benzothiazepines targeting GABA-A receptor as Anticonvulsant

Abstract

Epilepsy is a long-lasting condition of the nervous system that impacts around 50 million individuals across the globe. The condition is defined by repeated episodes of seizures, which can result in bodily harm, cognitive deficits, and emotional discomfort. Despite advances in the understanding and treatment of epilepsy, it remains a significant health burden globally. Currently, the management of epilepsy involves the use of antiepileptic drugs (AEDs), surgery, and lifestyle modifications. However, AEDs may cause side effects, and some people with epilepsy may not respond to them. In terms of research, there is ongoing work to identify new treatments for epilepsy, including non-invasive brain stimulation techniques, gene therapies, and new medications. In this study, 26 compounds were created using two distinct ring structures as their foundation and were tested for their in-silico activity (PDB ID: 6HUP). The objective was to target the GABAA receptor, using diazepam as the standard compound for comparison. Results showed that two of the newly designed compounds had significantly better docking scores when compared to the standard drug. These compounds also demonstrated strong hydrophobic interaction and binding affinity.