Synthesis, spectroscopic characterization, and antibacterial activity of chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one against multiresistant Staphylococcus aureus carrier of efflux pump mechanisms and ß-lactamase.

BACKGROUND: The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity. OBJECTIVES: In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties. METHODS: The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of ß-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100. RESULTS: The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 µg/mL, or on the enzymatic mechanism of ß-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 µg/mL. CONCLUSION: We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.

Antibacterial activity of eugenol on the IS-58 strain of Staphylococcus aureus resistant to tetracycline and toxicity in Drosophila melanogaster.

The indiscriminate use of antibiotics contributes significantly to the selection of bacteria resistant to several antibiotics. Among the resistance mechanisms are the Efflux Pumps which are responsible for extruding solutes from the cell cytoplasm through proteins in the cell membrane. Because of this, new strategies are needed to control multidrug-resistant pathogenic strains. In this way, the objective of this study was to evaluate the antibacterial activity of eugenol by inhibition of TetK Efflux Pump in strains of Staphylococcus aureus resistant to Tetracycline, in addition to evaluating its toxicity in Drosophila melanogaster. To determine the Minimum Inhibitory Concentration (MIC), the broth microdilution method was used. The modulated effect of antibiotic and Ethidium Bromide associated with eugenol in subinhibitory concentrations (MIC/8) was evaluated. To evaluate the toxic effect of eugenol on D. melanogaster, fumigation tests were used, in which the parameters of mortality and damage to the locomotor system were evaluated. The results showed that eugenol has no direct activity in S. aureus, with an MIC ≥1024 µg/mL. However, it demonstrated that the synergistic potential when associated with Tetracycline, reducing the MIC of the antibiotic, already associated with Ethidium Bromide, had an antagonistic effect. When the toxicity in D. melanogaster was evaluated, eugenol demonstrated a non-toxic profile, since it presented EC50: 2036 µL/mL in 48 h of exposure. In conclusion, eugenol had no relevant direct effect against S. aureus, however, it potentialized the action of the antibiotic by decreasing its MIC.

Phytochemistry and Biological Activities of Amburana cearensis (Allemão) ACSm.

Amburana cearensis (Allemão) ACSm. belongs to the Fabaceae family and occurs in the Brazilian semiarid, Argentina, Paraguay, Bolivia, and Peru. Numerous studies that portray its ethnobotany, use in popular medicine, chemical composition, and biological activities exist in the literature. This review aimed to provide an overview of the chemical composition, ethnopharmacology, and biological activities associated with A. cearensis and its isolated constituents. Information was collected from internet searches in the Scopus, Medline, PubMed, Google Scholar, and ScienceDirect databases were performed covering publications from 1997-2020. An ethnopharmacological literature analysis revealed that A. cearensis is used to treat a wide range of respiratory disorders in addition to intestinal, circulatory, and inflammatory problems. Coumarins, flavonoids, phenolic glycosides, phenolic acids, phenylpropanoid derivatives, and triterpenoids, among others, have been reported as active compounds, with High-Performance Liquid Chromatography (HPLC) being the main analytical technique used. The A. cearensis extracts and compounds presented several biological activities, including antimicrobial, antinociceptive, anti-inflammatory, antioxidant, neuroprotective, and myorelaxant activities, among others. This review provides a useful bibliography for future investigations and A. cearensis applications; however, future studies should focus on its toxic effects and the mechanisms of action of its extracts and isolated constituents to guide clinical applications.

Effect of estragole over the RN4220 Staphylococcus aureus strain and its toxicity in Drosophila melanogaster.

Among the bacterial resistance mechanisms, efflux pumps are responsible for expelling xenobiotics, including bacterial cell antibiotics. Given this problem, studies are investigating new alternatives for inhibiting bacterial growth or enhancing the antibiotic activity of drugs already on the market. With this in mind, this study aimed to evaluate the antibacterial activity of Estragole against the RN4220 Staphylococcus aureus strain, which carries the MsrA efflux pump, as well as Estragole's toxicity in the Drosophila melanogaster arthropod model. The broth microdilution method was used to perform the Minimum Inhibitory Concentration (MIC) tests. Estragole was used at a Sub-Inhibitory Concentration (MIC/8) in association with erythromycin and ethidium bromide to assess its combined effect. As for Estragole's toxicity evaluation over D. melanogaster, the fumigation bioassay and negative geotaxis methods were used. The results were expressed as an average of sextuplicate replicates. A Two-way ANOVA followed by Bonferroni's post hoc test was used. The present study demonstrated that Estragole did not show a direct antibacterial activity over the RN4220 S. aureus strain, since it obtained a MIC ≥1024 µg/mL. The association of estragole with erythromycin demonstrated a potentiation of the antibiotic effect, reducing the MIC from 512 to 256 µg/mL. On the other hand, when estragole was associated with ethidium bromide (EtBr), an antagonism was observed, increasing the MIC of EtBr from 32 to 50.7968 µg/mL, demonstrating that estragole did not inhibited directly the MsrA efflux pump mechanism. We conclude that estragole has no relevant direct effect over bacterial growth, however, when associated with erythromycin, this reduced its MIC, potentiating the effect of the antibiotic.