Antibacterial Potential of Ximenia americana L. Olacaceae: Molecular Docking, Molecular Dynamics, and ADMET Prediction

Introduction: The devastating effect of persistent and recurrent bacterial infections coupled with antibiotic resistance is a driving force for prospects into alternative antibacterial therapeutics to achieve treatment. This study investigates the antibacterial potential of Ximenia americana (XA) via molecular docking, molecular dynamics, and ADMET approach. Materials and methods: The ligands and target were downloaded from respective databases and docked using PyRx software followed by molecular dynamics simulation (MDS) with iMOD and CABflex 2.0 online servers then ADMET, drug likeness, lead likeness, and medicinal chemistry predictions of the top docked ligands using pkCSM and SwissADME online servers. Results: Stigmasterol exhibited the lowest binding affinity and inhibition constant respectively with all the targets; enoyl-acyl-carrier-protein reductase (-7.1 kcal/mol and 6.16 µM), Penicillin-binding Protein 2X (-8.8 kcal/mol and 0.35 µM), dihydrofolate reductase (-9.6 kcal/mol and 0.09 µM), dihydropteroate Synthase (-7.8 kcal/mol and 1.89 µM), UDP-N-acetylglucosamine enolpyruvyl transferase (-7.1 kcal/mol and 6.16 µM), and topoisomerase IV (-7.8 kcal/mol and 1.89 µM). The MDS showed several cluster displacements and residue fluctuations with the docked targets with higher residue fluctuations observed for enoyl-acyl-carrier-protein reductase (11.33 ?), Penicillin-binding Protein 2X (4.67 ?), dihydrofolate reductase (3.61 ?), dihydropteroate Synthase (4.97 ?), UDP-N-acetylglucosamine enolpyruvyl transferase (3.38 ?), and topoisomerase IV (4.35 ?). 4,4-Dimethylcyclohex-2-en-1-ol exhibited superior overall ADMET properties, oral bioavailability, drug-likeness, and medicinal chemistry. Conclusion: Conclusively, Stigmasterol and 4,4-Dimethylcyclohex-2-en-1-ol might be responsible for the antibacterial effect of XA. Although the latter showed better interaction with the target proteins, the former showed better ADMET properties, oral bioavailability, drug-likeness, and medicinal properties. However, improvement in these properties might enhance their antibacterial activity.