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.

Vector‐borne diseases remain a critical global health concern, particularly in tropical and subtropical regions, where socioeconomic conditions often favor vector proliferation. Pyriproxyfen, a juvenile hormone analog used as a larvicide against Aedes aegypti , is known for its fast‐acting efficacy, low toxicity, and favorable environmental profile. Because of these properties, pyriproxyfen was chosen as a reference scaffold to explore structurally and electrostatically similar compounds through ligand‐based virtual screening. The ChemBridge DIVERSet‐CL database (≈ 100,000 compounds) was used, applying ROCS for shape similarity and EON for electrostatic potential comparison. A total of 35 top‐ranked molecules were identified based on superior pharmacokinetic and toxicological properties compared with the reference. Subsequently, molecular docking analyses were performed to assess binding affinity and interaction modes with selected biological targets: acetylcholinesterase (AChE) and juvenile hormone‐binding proteins from various organisms. Two compounds, LMQC3 and LMQC23, demonstrated strong binding affinities to AChE enzymes from Drosophila melanogaster (−11.4 and −10.6 kcal/mol), Anopheles gambiae (−10.19 and −10.21 kcal/mol), and humans (−9.91 and −9.95 kcal/mol). Additionally, they exhibited high affinity toward the juvenile hormone protein in A. aegypti (−11.83 and −11.94 kcal/mol), surpassing reference ligands. Both molecules established key interactions with catalytic residues, supporting their potential dual inhibitory activity. These findings indicate that LMQC3 and LMQC23 are potential promising insecticidal candidates with multitarget potential, showing favorable predicted target‐binding profiles and encouraging in silico pharmacokinetic and toxicity characteristics. Their development could contribute to next‐generation mosquito control strategies and help mitigate the spread of arbovirus‐related diseases.

Processos circulares: ferramenta para resolução de conflitos pelas equipes de UBS do Amapá/ Circular processes: tool for conflict resolution by Amapá UBS teams

Antibiotic resistance among several bacteria is a warning sign that reinforces the need for research to identify new compounds that are effective against resistant strains. In this sense, bioinformatics stands out as an excellent tool for identifying drug candidates by using computational methodologies to detect compounds with potential biological activity. Two pivot compounds (QNZ and 0Y5) with biological activity against Staphylococcus aureus were selected. A virtual screening was performed in the MolPort database with a Tanimoto index of 0.5, resulting in 20,000 compounds, 10,000 compounds for each template. Then, methodologies were applied to calculate pharmacokinetic and toxicological parameters using Discovery Studio software; molecular docking via DockThor; lethal dose via ProTOX; lipophilicity, solubility, and Lipinski parameters via SwissADME; in silico prediction of bacterial activity via Way2Drug; theoretical synthetic accessibility via SwissADME and AMBIT-SA; and, finally, molecular dynamics simulations via AMBER 18. After the entire methodological process, 10 compounds were identified with potential results according to the criteria adopted in this study and with possible antimicrobial activity against resistant bacterial strains of S. aureus. Our theoretical findings suggest 10 potential candidates with possible antimicrobial activity against S. aureus and other genera and species of bacteria as these compounds presented excellent results using the proposed methodology. Certainly, more in vitro and in vivo study steps are necessary.

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.