Title:Molecular Docking and Modelling Studies for Identifying Novel Oxadiazole Derivatives to Inhibit COX-2 Enzyme as an Anti-Inflammatory Treatment
Volume: 22
Issue: 3
Author(s): Tarun Chaudhary*, Prabhat Kumar Upadhyay and Ritu Kataria
Affiliation:
- Department of Pharmaceutical Science, GLA University, Mathura - 281406, Uttar Pradesh, India
Keywords:
Molecular docking, oxadiazole, inflammation, molecular modelling, in-silico, heterocyclic compounds, chemistry, NSAIDs.
Abstract: The objective of the study was to develop new Oxadiazole compounds using docking
simulation studies for inhibitory action against the Cycloxoygenase-2(COX-2) enzyme. The study
aimed at the development and identification of novel and potent derivatives of 1,3,4-oxadiazole for
targeting anti-inflammatory disease by screening their inhibitory action against COX-2 enzyme with
schrodinger molecular docking software and molecular simulation by GROMACS 2022. A library of
375 novel compounds of 1,3,4-oxadiazoles derivatives was designed and proposed for docking
against cyclooxygenase-2 enzyme (COX-2)PDB ID: 6BL4, which was downloaded from protein
data bank site https://www.rcsb.org/. MD simulations for three models were performed, namely,
compound A-Cox-2, E-Cox-2, and G-Cox-2, for 100 ns. Out of 375 proposed compounds, the top 16
compounds with good docking scores and binding energy were selected for further ADME profile
studies in which all compounds showed good results as compared to Standard drugs. RMSD values
of 0.2 nm showed that all ligand-Cox-2 complexes were stable during simulation. Compound G was
the most efficient in decent interactions with the residues ARG120 and TYR355 of cyclooxygenase-
2, which were stable for 29.32, 21.52, and 12.00% duration of simulation along with comparatively
better h-bond contacts. All potential inhibitors met Lipinski's rule of five, indicating oral availability.
The potential compounds may be further evaluated for pharmacological activities using different in
vitro and in vivo evaluations.
