THEORETICAL STUDY OF MOLECULES DERIVED FROM BETA‑LACTAMS COMPOUNDS WITH POSSIBLE POTENTIAL ANTIBIOTIC ACTIVITY ON Staphylococcus aureus

Staphylococcus aureus is known worldwide as the principal cause of human bacterial infections; as well as methicillin-resistant Staphylococcus aureus (MRSA), is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. This work aims to carry out a theoretical study of molecules derived from beta-lactam compounds with possible potential antibiotic activity on Staphylococcus aureus. Therefore, computational chemistry tools were used to describe the interactions between potentially active molecules and the transpeptidase and beta-lactamase enzyme. These molecules were docked with transpeptidase and beta-lactamase enzymes, and all of them showed a higher affinity for transpeptidase (–4.81 kcal mol-1) than the reference molecule (methicillin), but only two showed a lower affinity for beta-lactamase (–6.8 kcal mol-1). The two ligands that presented the best ranking docking results were subjected to molecular dynamics simulations to assess conformational stability through root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analysis. According to simulation, the ligands that bind to the proteins do not cause significant conformational changes in the structures of the proteins. The absorption, distribution, metabolism, and excretion (ADME) properties of the molecules with the lowest affinity for beta-lactamase were estimated. The ADME properties predict that the molecules would have good bioavailability.