In silico discovery of potential azole-containing mPGES-1 inhibitors by virtual screening, pharmacophore modeling and molecular dynamics simulations

Inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) is promising for designing novel nonsteroidal anti-inflammatory drugs, as they lack side-effects associated with inhibition cyclooxygenase enzymes. Azole compounds are nitrogen-containing heterocycles and have a wide use in medicine considered medicinal chemistry. Various computer-aided drug design strategies incorporated this study. Structure-based virtual screening was performed employing various docking programs. Receiver operator characteristic (ROC) curves were used to evaluate the selectivity each program. Furthermore, scoring power Autodock4 Autodock Vina assessed by Pearson’s correlation coefficients. Pharmacophore models generated Güner-Henry score best model calculated 0.89. Binding modes final 10 azole analyzed further investigation binding (− 8.38 kcal/mol) compound using molecular dynamics simulation, revealing that furazan1224 (ZINC001142847306) occupied site substrate, H2 (PGH2) remained stable 100 ns. Continuous hydrogen bonds hydrophobic interactions amino acids active supported stability throughout trajectory. Pharmacokinetic profile showed lacks risks inhibiting cytochrome P450 3A4 enzyme central nervous system-related side-effects.