Molecular Docking Studies of Tribulus Terrestris Phytochemicals Against Bovine Mastitis Caused by Methicillin-resistant Staphylococcus Aureus

Bovine mastitis caused by methicillin-resistant Staphylococcus aureus is among the diseases capable of transferring from animal to human. It often leads to the development of antibiotic-resistant genes in both humans and animals. It is marked by the failure of the active-serine site of the blaZ gene in association with mecA to hydrolyze antibiotics which will inhibit the production of the beta-lactamase enzyme. This research aims to assess the interactions and binding affinities of Tribulus terrestris phytochemicals and important bacterial proteins involved in bovine mastitis. The research process begins with the identification of important bacterial proteins responsible for bovine mastitis and then the preparation of protein and ligand structures. Consequently, docking was performed, and interactions between protein-ligand were analyzed and visualized. Four phytoconstituents of Tribulus Terrestris (2,7-Diphenyl-1,6-dioxopyridazino [4,5:2',3'] pyrrolo [4',5'] pyridazine, gitogenin, tigogenin, and hecogenin) were chosen, and molecular docking simulations revealed all the four compounds exhibit good binding affinities. The docking scores of the ligands with blaZ are as follows; 2,7-Diphenyl-1,6-dioxopyridazino [4,5:2',3'] pyrrolo [4',5'] pyridazine (-7.9), gitogenin (-8.9), tigogenin (-8.9) and hecogenin (-9.0). Also, the docking scores of the ligands with mecA are as follows; 2,7-Diphenyl-1,6-dioxopyridazino [4,5:2',3'] pyrrolo [4',5'] pyridazine (-9.4), gitogenin (-6.4), tigogenin (-6.5) and hecogenin (-6.8). Based on the predicted ADMET values using the Lipinski and Veber rule, compounds with potentially good activities were identified. The results suggest that only tigogenin is likely to exhibit antibacterial activity by binding with the active-serine site of blaZ