In silico study demonstrates stable binding of novel pyrazole derivatives to cyclooxygenase-2, highlighting candidates 3b, 3d, and 3g for anti-inflammatory drug design.
Key Points
To evaluate the binding interactions and dynamic stability of novel 4-difluoromethyl pyrazole derivatives (3a–3h) as prospective cyclooxygenase-2 (COX-2) inhibitors for anti-inflammatory drug discovery.
Conducted molecular docking simulations of compounds 3a–3h into the murine COX-2 active site (PDB ID: 3LN1) to determine static binding modes and affinities.
Performed density functional theory (DFT) calculations for frontier molecular orbital energies and molecular electrostatic potential surfaces, alongside molecular dynamics (MD) simulations to assess stability.
Static docking identified compounds 3a and 3f as having the highest initial binding affinity via three hydrogen bonds and hydrophobic contacts, while compound 3g achieved a binding energy of −6.98 kcal/mol.
Molecular dynamics simulations revealed that compounds 3a and 3f exhibited only moderate stability under dynamic conditions, whereas compounds 3b, 3d, and 3g displayed superior stability across multiple metrics.