Molecular Docking and ADME Profiling of N-(Substituted-1,3-benzothiazol-2-yl)benzamide Derivatives as Potential Anticonvulsant Agents
TL;DR
The docking analysis suggest that selected N-(substituted-1,3-benzothiazol-2-yl)benzamide derivatives, particularly Cp1, Cp3, Cp7, Cp10, Cp12, Cp13, and Cp14 were identified as the most promising lead candidates, with significant potential for anticonvulsant activity.
Abstract
Amides represent a class of organic compounds with a variety of biological potential and anticonvulsant properties.This study aimed to evaluate the pharmacokinetic properties and molecular interactions of 15 N-(substituted-1,3-benzothiazol-2-yl)benzamide derivatives with two key epilepsy-related targets, γ-aminobutyric acid aminotransferase (GABA-AT) and activated open sodium ion channel proteins, in order to assess their potential anticonvulsant activity. Crystal structures of GABA-AT (PDB ID: 1OHW) and the sodium ion channel (PDB ID: 5HVX) were obtained from the RCSB Protein Data Bank. Molecular docking was performed using AutoDock Vina following protein preparation in Chimera v1.11.2. Post-docking analysis was conducted using Chimera and Discovery Studio Visualizer. ADME properties were also predicted. ADME analysis showed high gastrointestinal absorption for all compounds except compound 5. Docking results revealed that seven compounds (Cp1, Cp3, Cp7, Cp10, Cp12, Cp13, and Cp14) exhibited interaction profiles similar to vigabatrin, while three (Cp10, Cp13, and Cp14) aligned with lamotrigine. These compounds demonstrated favorable binding interactions with both targets. The docking analysis suggest that selected N-(substituted-1,3-benzothiazol-2-yl)benzamide derivatives, particularly Cp1, Cp3, Cp7, Cp10, Cp12, Cp13, and Cp14 were identified as the most promising lead candidates, with significant potential for anticonvulsant activity.