DESIGN AND MOLECULAR DOCKING STUDIES OF N1-CHLOROACETYL-7-SUBSTITUTED- 4-METHYL-1, 5-BENZODIAZEPINE-2-ONE DERIVATIVESAbstract
Molecular Docking is an effective and competent tool for in-silico screening. It is playing an important and ever-increasing role in rational drug design. The main application lies in this structure-based virtual screening is the identification of new active compounds towards a particular target protein. In present investigation, few N1-chloroacetyl-7-substituted- 4-methyl-1, 5-benzodiazepine-2-one and 7-Substituted-4-methyl-1,5-benzodiazepin-2-one are designed and docked at active site of cavity 1# of GABA-A receptor-associated protein (1KJT) to identify their hypothetical binding mode. As a target protein, we used the X-ray crystal structure of mammalian GABA-A receptor-associated protein from the Protein Data Bank. The Molecular Design Suite was used in this study to conduct docking investigations and conformational analyses. The comparative docking experiments of designed compounds with known GABA agonist, Clobazam was carried out. The dock scores calculated for Clobazam was -5.2598. Among the designed compounds, following conformation were found to have lower dock scores as indicated in bracket; N1-chloroacetyl-7-bromo-4-methyl-1,5-benzodiazepine-2-one, Conformer_C4 (-4.7869) and 7-chloro-4-methyl-1,5-benzodiazepin-2-one, Conformer_C13 (-5.0485) and said to have better affinity for active site of GABA-A receptor-associated protein than other molecules.
Dinesh Rishipathak *, Dipak Patil and Manisha Raut
Department of Pharmaceutical Chemistry, MET’s Institute of Pharmacy, Bhujbal Knowledge City, Nashik, Maharashtra, India.
26 December 2021
02 March 2022
30 April 2022
01 August 2022