Molecular docking and DFT study of 4-difluoromethyl pyrazole derivatives as cyclooxygenase-2 inhibitor

We applied molecular docking simulations and DFT to examine the binding interactions of 4-difluoromethyl pyrazole derivatives ( 3a-3h ). We assessed the potential binding mechanisms and strengths of derivatives within the receptor's binding site. By methodical simulations, we elucidated the characteristics and interactions towards binding capacities. Proposed compounds were subjected to molecular docking with the major protease ( PDB:3LN1 ) to assess binding affinities. In designed compounds ( 3a-3h ), 3a and 3f show the highest docking score, leading to high affinity toward 3LN1 . An energy score of -6.9765 Cal/mol of ligand 3g suggests a strong and advantageous binding affinity, with the negative number indicating stability. The reactivity parameters, FMO, and MEP of the drugs were estimated by DFT calculations. The strong affinity of 3a and 3f was attributed to the existence of three hydrogen bonds and several hydrophobic interactions between the drug and the essential amino acid residues of the receptor. Ultimately, the molecular docking findings were illustrated using the estimated molecule electrostatic potential data using DFT. All these characteristics showed varying degrees of influence on the binding affinity of these compounds with the active protein locations.