Open AccessMolecular Modelling of 1H-Benzo [b] [1,5] Diazepine-2(3H)-one Derivatives and Docking Studies Against Receptor Associated Protein
Author(s) -
Dinesh Rishipathak,
Dipak V. Patil,
Komal Ushir
Publication year - 2022
Publication title -
journal of pharmaceutical research international
Language(s) - English
Resource type - Journals
ISSN - 2456-9119
DOI - 10.9734/jpri/2022/v34i21a35838
Subject(s) - conformational isomerism , docking (animal) , dock , chemistry , stereochemistry , agonist , diazepine , receptor , gabaa receptor , molecule , biochemistry , medicine , ring (chemistry) , organic chemistry , nursing
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.