Novel pyrimidines as COX-2 selective inhibitors: synthesis, DFT analysis, molecular docking and dynamic simulation studies.

Pyrimidine and its derivatives are associated with varieties of biological properties. Therefore, we herein reported the synthesis of four novel pyrimidines (, , and ) derivatives. The structure of these molecules is confirmed by spectroscopic methods such as IR, NMR, and Mass analysis. The electronic behavior of synthesized compounds and in silico drug design was explained by Density Functional Theory estimations at the DFT/B3LYP level 6-31 G++ (d, p) replicates the structure and geometry. All the synthesized compounds were screened for their COX-1 and COX-2 inhibitory activity compared to standards Celecoxib and Ibuprofen. Compounds and afforded excellent COX-1 and COX-2 inhibitory activities at IC = 5.50 and 5.05 μM against COX-1, 0.85 and 0.65 μM against COX-2, respectively. The standard drugs Celecoxib and Ibuprofen showed inhibitory activity at IC = 6.34 and 3.1 μM against COX-1, 0.56 and 1.2 μM against COX-2, respectively. Further, these compounds showed high potential docking with SARS-CoV-2 Omicron protease & COX-2 and predicted drug-likeness for the pyrimidine analogs by using Molinspiration. The protein stability, fluctuations of APO-protein, protein-ligand complexes were investigated through Molecular Dynamics simulations studies using Desmond Maestro 11.3 and potential lead molecules were identified.Communicated by Ramaswamy H. Sarma.