Ana Carolina Justino de Araújo

Background/Objectives: Synthetic compounds, particularly thiadiazine derivatives with antibacterial properties, have emerged as promising candidates in addressing the growing challenge of bacterial multidrug resistance. Thiadiazine derivatives are six-membered heterocyclic compounds containing two nitrogen atoms and one sulfur atom, exhibiting diverse medical and pharmacological activities. This study aimed to evaluate the potentiating activity of thiadiazine derivatives against multidrug-resistant bacteria. Methods: ADMET (absorption, distribution, metabolism, excretion, and toxicity) assays were performed to assess similarity with more than 370,000 three-dimensional structures of bioactive compounds. The multidrug-resistant bacterial strains Staphylococcus aureus 10 and Pseudomonas aeruginosa 24 were used to investigate both the direct antibacterial activity and the antibiotic-modifying activity of thiadiazine derivatives. Results: The thiadiazine analogs did not exhibit direct antibacterial activity, presenting a minimum inhibitory concentration of 1024 μg/mL. However, they demonstrated a significant antibiotic-modifying effect, potentiating the activity of conventional antibiotics, particularly norfloxacin, against the tested strains. In silico analyses indicated that the analogs predominantly exhibited affinity for G protein-coupled receptors and possessed physicochemical characteristics compatible with potential drug candidates. Conclusions: Although the evaluated thiadiazine derivatives lacked direct antibacterial activity, they significantly enhanced the efficacy of antibiotics against multidrug-resistant bacteria. Combined with their favourable in silico pharmacokinetic and physicochemical profiles, these findings suggest that thiadiazine derivatives may represent promising antibiotic adjuvants for combating multidrug-resistant bacterial infections.

Background: Substances with antibacterial properties have become crucial in light of the continuous increase in infections caused by multidrug-resistant bacteria. In this context, thiadiazines have emerged as heterocyclic compounds already known for their pharmacological activities. However, their potential as antibacterial agents and inhibitors of the efflux system found in resistant bacteria remains poorly understood. From this perspective, the present study highlights the synthesis of thiadiazine-derived compounds and evaluates their antibacterial activity and efflux pump inhibition against the Staphylococcus aureus 1199B strain. Methods: To this end, Minimum Inhibitory Concentration (MIC) tests were conducted, along with the analysis of antibacterial activity through the inhibition of the NorA efflux system using 96-well microdilution assays. Additionally, to assess efflux system inhibition, ethidium bromide (EtBr) fluorescence emission tests were performed, alongside in silico molecular docking studies. Results: Based on the results obtained, it was observed that compound IJ28 exhibited direct activity against the tested SA 1199B strains, with an MIC of 512 µg/mL. It also demonstrated antibacterial activity through efflux pump inhibition, resulting in increased fluorescence rates emitted by EtBr. Compound IJ28 showed a more significant reduction in the Minimum Inhibitory Concentration (MIC) of ethidium bromide, decreasing from 26.6 µg/mL to 0.5 µg/mL, compared to the other compounds. Conclusions: Therefore, it is essential to conduct further studies to investigate the mechanism of action and clarify the feasibility and effects of compound IJ28 as a potential antibacterial agent.

Substances with antibacterial properties have become crucial in light of the continuous increase in infections caused by multidrug-resistant bacteria. In this context, thiadiazines have emerged as heterocyclic compounds already known for their pharmacological activities. However, their potential as antibacterial agents and inhibitors of the efflux system found in resistant bacteria remains poorly understood. From this perspective, the present study highlights the synthesis of thiadiazine-derived compounds and evaluates their antibacterial activity and efflux pump inhibition against the Staphylococcus aureus 1199B strain. To this end, Minimum Inhibitory Concentration (MIC) tests were conducted, along with the analysis of antibacterial activity through the inhibition of the NorA efflux system using 96-well microdilution assays. Additionally, to assess efflux system inhibition, ethidium bromide (EtBr) fluorescence emission tests were performed, alongside in silico molecular docking studies. Based on the results obtained, it was observed that compound IJ28 exhibited direct activity against the tested SA 1199B strains, with an MIC of 512 µg/mL. It also demonstrated antibacterial activity through efflux pump inhibition, resulting in increased fluorescence rates emitted by EtBr. Compound IJ28 showed a more significant reduction in the Minimum Inhibitory Concentration (MIC) of ethidium bromide, decreasing from 26.6 µg/mL to 0.5 µg/mL, compared to the other compounds. Therefore, it is essential to conduct further studies to investigate the mechanism of action and clarify the feasibility and effects of compound IJ28 as a potential antibacterial agent.

This study set out to evaluate how effective the unexplored macrofungi Langermannia bicolor is in providing a biomolecular repertoire capable of optimizing the action of antibacterials available on the market. Extract and fractions (obtained by fractionation with acetone) of L. bicolor were quantified for the presence of proteases and hemagglutinin, and the composition of carbohydrates, proteins, and phenolic and flavonoid compounds; then, they were tested against multidrug-resistant gram-positive and gram-negative strains combined with conventional antibiotics from different classes. Fraction 2 (F2) stood out for its high proteolytic and hemagglutinating capacities, and could reduce the therapeutic dosage of all the antibiotics in the different pathogens tested. The samples – especially Fraction 2 – showed promising results in optimizing the action of antibiotics, thus potentially mitigating the escalation of resistance in bacteria. This project is the first to investigate the medicinal properties of L. bicolor, focusing on its major biomolecules, and potential as an antibiotics enhancer.

Objective: The study aimed to optimize protocols for the joint extraction of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from 0.025 × 10⁶ CFU of Candida albicans, targeting to overcome the challenges in the extraction of these genetic materials. Materials and methods: From this, treated silicon carbide (SiC) granules were added to fungal samples from methods 1, 2, and 3 obtained from aliquots of BHI or Sabouraud medium to cause cell lysis and enable the isolation of these macromolecules by phenol and chloroform. The concentration and integrity of the extracted nucleic acids were analyzed, respectively, by spectrophotometry using the A₂₆₀/A₂₈₀ ratios and 1% agarose gel electrophoresis. Results: Therefore, method 3 is the one that most comprises samples considered pure of both DNA and RNA, simultaneously. Furthermore, the presence of intact RNAs corresponding to the base pair size such as 5.8 S rRNA and tRNA was verified during electrophoresis, considering the particularities of RNA, which makes it very unstable and easily degraded. Conclusions: Thus, it results in a faster and simpler method in addition to obtain promising results using minimal amounts of biological sample and offering a valuable alternative for small laboratories to work with molecular biology.

The study aimed to optimize protocols for the joint extraction of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from 0.025 x 106 CFU of Candida albicans, aiming to overcome challenges in the extraction of these genetic materials. From this, treated Silicon Carbide (SiC) granules were added to fungal samples from methods 1, 2 and 3 obtained from aliquots of BHI or Sabouraud medium to cause cell lysis and enable the isolation of these macromolecules by phenol and chloroform. The concentration and integrity of nucleic acids were obtained, respectively, by spectrophotometry using A260/A280 ratios and 1% agarose gel electrophoresis. Therefore, method 3 is the one that most comprises samples considered pure of both DNA and RNA, simultaneously. Furthermore, the presence of intact RNAs corresponding to the base pair size, such as 5.8 S rRNA and tRNA, was verified during electrophoresis, taking into account the particularities of RNA, which makes it very unstable and easily degraded. Therefore, it results in a faster and simpler method in addition to obtaining promising results using minimal amounts of biological sample, thus offering a valuable alternative for small laboratories working with molecular biology.

In recent decades, acceptance of nanoparticles (NPs) in therapeutic applications has increased because of their outstanding physicochemical features. By overcoming the drawbacks of conventional therapy, the utilization of metal NPs, metal-oxide, or metal supported nanomaterials have shown to have significant therapeutic applications in medicine. This is proved by a lot of clinical and laboratory investigations that show improved treatment outcomes, site-specific drug delivery, and fewer side effects compared to traditional medicine. The metal NPs interaction with living cells (animal and plant) showed many ways to develop therapeutic models with the NPs. Despite all of the advancements that science has achieved, there is still a need to find out their performance for long-term use to solve modern challenges. In this regard, the present documentation reviews some potential metals, including silver (Ag), gold (Au), zinc (Zn), copper (Cu), iron (Fe), and nickel (Ni) NPs, as therapeutic agents in various areas such as anticancer, antimicrobial, antidiabetic, and applicable for the treatment of many other diseases. Depending on the outstanding ongoing research and practical trials, metal-based NPs can be considered the hope of prospective modern therapeutic areas.

Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus are the primary bacteria that cause clinical infections, such as urinary and intestinal infections, pneumonia, endocarditis, and sepsis. Bacterial resistance is an innate natural occurrence in microorganisms, resulting from mutations or the lateral exchange of genetic material. This serves as evidence for the association between drug consumption and pathogen resistance. Evidence has demonstrated that the association between conventional antibiotics and natural products is a promising pharmacological strategy to overcome resistance mechanisms. Considering the large body of research demonstrating the significant antimicrobial activities of Schinus terebinthifolius Raddi, the present study aimed to evaluate the chemical composition and antibiotic-enhancing effects of Schinus terebinthifolius Raddi essential oil (STEO) against the standard and multidrug-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The STEO was extracted by hydrodistillation using a Clevenger-type vacuum rotary evaporator. The Minimum Inhibitory Concentration (MIC) of the STEO was assessed by the microdilution method to evaluate the antibacterial activity. The antibiotic-enhancing activity of the essential oil was assessed by determining the MIC of antibiotics in the presence of a sub-inhibitory concentration (MIC/8) of the natural product. The GC-MS analysis revealed alpha-pinene (24.3%), gamma-muurolene (16.6%), and myrcene (13.7%) as major constituents of the STEO. The STEO potentiated the enhanced antibacterial activity of norfloxacin and gentamicin against all the strains and increased the action of penicillin against the Gram-negative strains. Therefore, it is concluded that although the STEO does not exhibit clinically effective antibacterial activity, its association with conventional antibiotics results in enhanced antibiotic activity.

Background: Pathogenic microorganisms are causing increasing cases of mortality and morbidity, along with alarming rates of ineffectiveness as a result of acquired antimicrobial resistance. Bi₂WO₆ showed good potential to be used as an antibacterial substance when exposed to visible light. This study demonstrates for the first time the dimension-dependent antibacterial activity of layered Bi₂WO₆ nanosheets. Materials and methods: The synthesized layered Bi₂WO₆ nanosheets were prepared by the hydrothermal method and characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), and Raman and Fourier transform infrared spectroscopy (FTIR). Antibacterial and antibiotic-modulation activities were performed in triplicate by the microdilution method associated with visible light irradiation (LEDs). Results: Bi₂WO₆ nanosheets were effective against all types of bacteria tested, with MIC values of 256 μg/mL against Escherichia coli standard and resistant strains, and 256 μg/mL and 32 μg/mL against Staphylococcus aureus standard and resistant strains, respectively. Two-dimensional (2D) Bi₂WO₆ nanosheets showed antibacterial efficiency against both strains studied without the presence of light. Conclusions: Layered Bi₂WO₆ nanosheets revealed dimension-dependent antibacterial activity of the Bi₂WO₆ system.