Molecular Modelling of 1H-Benzo [b] [1,5] Diazepine-2(3H)-one Derivatives and Docking Studies Against Receptor Associated Protein

Abstract

In the present investigation, some N1-benzoyl/ N1-(1,3,4-thiadiazol-2-yl amino acetyl) -7-substituted- 4-methyl-1,5-benzodiazepine-2-one were designed and docked at active site of cavity 1# of GABA-A receptor associated protein (1KJT) to distinguish from their hypothetical binding mode. The X-ray crystal structure of mammalian GABA-A receptor associated protein (1KJT) obtained from protein data bank was used as target protein. In this investigation the comparative analysis of the docking experiments of modelled compounds with known GABA agonist, Lofendazam was carried out. The dock scores calculated for Lofendazam was -4.7373. Among the modelled compounds, following conformation were found to have lower dock scores as indicated in bracket in comparison to other confermers; N1-benzoyl-7- bromo- 4-methyl-1,5-benzodiazepine-2-one, conformer_C3 (-5.0915), N1-(1,3,4-thiadiazol-2-yl amino acetyl) -7-chloro-4-methyl-1,5-benzodiazepine-2-one, Conformer_C2 (-4.6532). These conformers have more affinity for active site of GABA-A receptor associated protein than other molecules.