In silico ADMET, toxicological analysis, molecular docking studies and Molecular dynamics simulation of Afzelin with potential antibacterial effects against Staphylococcus aureus

Afzelin has been designed and tested for its in silico antibacterial activity against DNA gyrase complex of Staphyloccocus aureus. The results of the toxicity study indicate that afzelin displayed moderate antibacterial potential against staphylococcus aureus with LD50 = 5000 mg/Kg, which is almost four times and a half weaker than that obtained for the commercial antibiotic chloramphenicol. The afzelin and the commercial antibiotic chloramphenicol were subjected to docking studies to understand their interaction with DNA gyrase complex of Staphyloccocus aureus. Results indicated a good affinity of afzelin to the chosen target with the formation of four hydrogen bonds and binding energy of 29.82 KJ/mol. ADME study shows that afzelin is not inhibitors of CYP450 IA2, 2C19, 2C9, 2D6, 3A4 isoenzymes which suggests a decrease in their plasma concentrations and a rapid elimination route. Molecular dynamics simulations were performed for 10 ns for afzelin using the gromacs package to assess the conformational stability of protein-ligand complexes during the simulation.