Staphylococcus aureus is a microorganism with high morbidity and mortality due to antibiotic-resistant strains, making the search for new therapeutic options urgent. In this context, computational drug design can facilitate the drug discovery process, optimizing time and resources. In this work, computational methods involving ligand- and structure-based virtual screening were employed to identify potential antibacterial agents against the S. aureus MRSA and VRSA strains. To achieve this goal, tetrahydroxybenzofuran, a promising antibacterial agent according to in vitro tests described in the literature, was adopted as the pivotal molecule and derivative molecules were considered to generate a pharmacophore model, which was used to perform virtual screening on the Pharmit platform. Through this result, twenty-four molecules were selected from the MolPort^® database. Using the Tanimoto Index on the BindingDB web server, it was possible to select eighteen molecules with greater structural similarity in relation to commercial antibiotics (methicillin and oxacillin). Predictions of toxicological and pharmacokinetic properties (ADME/Tox) using the eighteen most similar molecules, showed that only three exhibited desired properties (LB255, LB320 and LB415). In the molecular docking study, the promising molecules LB255, LB320 and LB415 showed significant values in both molecular targets. LB320 presented better binding affinity to MRSA (−8.18 kcal/mol) and VRSA (−8.01 kcal/mol) targets. Through PASS web server, the three molecules, specially LB320, showed potential for antibacterial activity. Synthetic accessibility (SA) analysis performed on AMBIT and SwissADME web servers showed that LB255 and LB415 can be considered difficult to synthesize and LB320 is considered easy. In conclusion, the results suggest that these ligands, particularly LB320, may bind strongly to the studied targets and may have appropriate ADME/Tox properties in experimental studies.

The study performed quantum chemical calculations of four flavonoids (Chalcone, Flavone, Isoflavone and Aurone) and a synthetic derivative (Isoxazolone) to evaluate their antioxidant and antimicrobial potentialities in comparison to the compound (E)-3-(2-(4-cyanostyryl)-4-oxoquinazolin-3(4H)-yl)benzoic acid, QNZ, known for its activity against antibiotic-resistant Staphylococcus aureus. The calculations were performed using Density Functional Theory (DFT) on the B3LYP/6-311G(d,p) and B3LYP/6-311++G(2d,2p) bases. The descriptors obtained included HOMO, LUMO, GAP and Ionization Potential (IP). The results indicated that Aurone presented the lowest GAP, suggesting high reactivity, while QNZ stood out for its electron donation (HOMO) and electron acceptance (LUMO) capacity, presenting results similar to flavonoids. The Tanimoto Index revealed low structural similarity between QNZ and the other compounds, except for Isoxazolone. The results suggest that flavonoids and Isoxazolone may be potential antioxidants and antimicrobial candidates, justifying new in vitro assays to evaluate the antimicrobial activity against resistant strains.