Investigating the inhibitory effect of new imidazole derivatives on cyclooxygenase II enzyme with computational approach

Mollaie, Zeinab; Karami, Leila; Rezaee, Elham; Karimi, Gilda

Volume 10, Issue 3 (12-2023) nbr 2023, 10(3): 169-183 | Back to browse issues page

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Mollaie Z, Karami L, Rezaee E, Karimi G. Investigating the inhibitory effect of new imidazole derivatives on cyclooxygenase II enzyme with computational approach. nbr 2023; 10 (3) :169-183
URL: http://nbr.khu.ac.ir/article-1-3632-en.html

Investigating the inhibitory effect of new imidazole derivatives on cyclooxygenase II enzyme with computational approach

Zeinab Mollaie

, Leila Karami ^*

, Elham Rezaee

, Gilda Karimi

Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran , l_karami@khu.ac.ir

Abstract: (2161 Views)

It has been found that the second isoform of COX enzyme known as COX-2 plays an important role in inflammation and rheumatoid arthritis and osteoarthritis. Thus, designing COX-2 inhibitors to treat inflammation is among the most important goals of researchers. In this study, the inhibitory effect of 3 new imidazole derivatives on COX-2 was evaluated by in silico approach. Molecular docking was done using Autodock Vina and the best binding mode of inhibitors was used as input of molecular dynamics (MD) simulation. MD was performed using Gromacs software for 120 ns. Then, structural and thermodynamic analyzes (ΔG_binding) and prediction of physicochemical properties were performed. RMSD data showed the compounds reached a good equilibrium and had favorable stability during simulation. Also, the RMSF showed that due to binding of inhibitors, the fluctuations of complexes decreased and the active site residues had the lowest amount. Rg, SASA and DSSP analysis showed that the protein structure did not change significantly. It was also found that Ser530 and Tyr355 residues play a more effective role in hydrogen bond formation. Physicochemical parameters determined the good drug-likeness properties for all compounds. Structural and thermodynamic analyzes (MM-PBSA) and IC₅₀ data indicate the favorable inhibitory effect of compound 5b.

Keywords: binding free energy, COX-2 inhibitors, inflammation, molecular docking, molecular dynamics simulation

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