RESUMO
Antimicrobials fight microorganisms, preventing and treating infectious diseases. However, antimicrobial resistance (AMR) is a growing concern due to the inappropriate and excessive use of these drugs. Several mechanisms can lead to resistance, including efflux pumps such as the NorA pump in Staphylococcus aureus, which reduces the effectiveness of fluoroquinolones. Thiadiazines are heterocyclic compounds whose chemical structure resembles that of cephalosporins. Therefore, these compounds and their derivatives have been studied for their potential in combating increased bacterial resistance. To analyze this hypothesis, direct activity assays, antibiotic action-modifying activity, fluorescence assays to evaluate the retention of ethidium bromide inside bacteria, and molecular docking were carried out. These experiments involved serial dilutions in microplates against Staphylococcus aureus strain 1199B under the influence of six thiadiazine derivatives (IJ10, IJ11, IJ21, IJ22, IJ23, and IJ25). The tests revealed that, despite not showing effective direct activity, some thiadiazine derivatives (IJ11, IJ21, and IJ22) inhibited the function of the bromide pump both in microdilution tests and in fluorescence and docking assays. Particularly, the IJ11 compound stood out for its activity similar to efflux inhibitors, as well as its inhibition of the norfloxacin pump of this bacterium. Among the results of this study, it deserves to be highlighted for anchoring future experiments, as it represents the first investigation of this group of thiadiazine derivatives against the NorA pump.
Assuntos
Antibacterianos , Proteínas de Bactérias , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Staphylococcus aureus , Tiadiazinas , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/química , Tiadiazinas/farmacologia , Tiadiazinas/química , Simulação por ComputadorRESUMO
Multidrug resistance is a significant health problem worldwide, with increasing mortality rates, especially in the last few years. In this context, a consistent effort has been made to discover new antibacterial agents, and evidence points to natural products as the most promising source of bioactive compounds. This research aimed to characterize the antibacterial effect of the essential oil of Etlingera elatior (EOEE) and its major constituents against efflux pump-carrying Staphylococcus aureus strains. The essential oil was extracted from fresh inflorescences by hydrodistillation. Chemical analysis was performed using gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography equipped with a flame ionization detector (GC-FID). The strains RN-4220, 1199B, IS-58, and 1199 of S. aureus were used to evaluate the antibacterial activity and the inhibition of efflux pumps. A total of 23 compounds were identified, including dodecanal and 1-dodecanol as major compounds. EOEE and dodecanal showed weak activity against the strains, while 1-dodecanol inhibited bacterial growth at low concentrations, indicating strong antibacterial activity. In addition, this compound potentiated the activity of norfloxacin against S. aureus 1199. In conclusion, 1-dodecanol was identified as the most effective compound of EOEE, showing significant potential to be used in antibacterial drug development.
Assuntos
Óleos Voláteis , Staphylococcus aureus , Cromatografia Gasosa-Espectrometria de Massas , Antibacterianos/farmacologia , Antibacterianos/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Dodecanol/farmacologiaRESUMO
The increased resistance of microorganisms to antimicrobial drugs makes it necessary to search for new active compounds, such as chalcones. Their simple chemical structure makes them molecules easy to synthesize. Therefore, the aim of this study was to evaluate the antimicrobial and potentiating activity of antibiotics and antifungals by synthetic chalcones against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. The synthesis of chalcones was carried out by Claisen-Schimidt aldol condensation. Nuclear Magnetic Resonance (NMR) and Gas Chromatography Coupled to Mass Spectrometry (GC/MS) were also performed. Microbiological tests were performed by the broth microdilution method, using gentamicin, norfloxacin and penicillin as standard drugs for the antibacterial assay, and fluconazole for the antifungal assay. Three chalcones were obtained (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one (DB-Acetone), (1E,3E,6E,8E)-1,9-diphenylnone-1,3,6,8-tetraen-5-one (DB-CNM), (1E,4E)-1,5-bis (4-methoxyphenyl) penta-1,4-dien-3-one (DB-Anisal). The compound DB-Acetone was able to inhibit P. aeruginosa ATCC 9027 at a concentration of 1.4 × 102 µM (32 µg/mL), while DB-CNM and DB-Anisal inhibited the growth of S. aureus ATCC 25923 at 17.88 × 102 µM and 2.71 × 101 µM (512 µg/mL and 8 µg/mL) respectively. In the combined activity, DB-Anisal was able to potentiate the effect of the three antibacterial drugs tested against E. coli 06, norfloxacin (128 for 4 µg/mL ±1) against P. aeruginosa 24 and penicillin (1,024 for 16 µg/mL ±1) against S. aureus 10. In antifungal assays, chalcones were not able to inhibit the growth of fungal strains tested. However, both showed potentiating activity with fluconazole, ranging from 8.17 x 10-1 µM (0.4909 µg/mL) to 2.35 µM (13.96 µg/mL). It is concluded that synthetic chalcones have antimicrobial potential, demonstrating good intrinsic activity against fungi and bacteria, in addition to potentiating the antibiotics and antifungal tested. Further studies are needed addressing the mechanisms of action responsible for the results found in this work.
Assuntos
Anti-Infecciosos , Chalconas , Antifúngicos/química , Fluconazol/farmacologia , Chalconas/farmacologia , Chalconas/química , Staphylococcus aureus , Norfloxacino/farmacologia , Escherichia coli , Acetona/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/química , Candida albicans , Penicilinas/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Artocarpus heterophyllus (jackfruit) is an evergreen tree distributed in tropical regions and is among the most studied species of the genus Artocarpus. The jackfruit almond has been highlighted in relation to phytochemical studies, biological properties, and application in the development of food products. This study aimed to analyze jackfruit fixed oil regarding chemical components, antibacterial property alone, and in association with antibiotics against standard and MDR bacteria strains. In the analysis of the oil by gas chromatography coupled to a flame ionization detector (GC-FID), a high content of saturated fatty acids (78.51%) was identified in relation to unsaturated fatty acids (17.07%). The main fatty acids identified were lauric acid (43.01%), myristic acid (11.10%), palmitic acid (6.95%), and oleic acid (15.32%). In the antibacterial analysis, broth microdilution assays were used. The oil presented minimum inhibitory concentration (MIC) ≥ 1024 µg/mL in antibacterial analysis for standard and MDR bacterial strains. The oil showed synergistic effects in the association with gentamicin, ofloxacin, and penicillin against MDR strains, with significant reductions in the MIC of antibiotics. The results suggest that the fixed oil of A. heterophyllus has fatty acids with the potential to synergistically modify antibiotic activity.
RESUMO
Essential oils are secondary metabolites with immense pharmacological potential.These substances are abundantly produced by plants of the family Asteraceae, such as Baccharis coridifolia. Previous studies have demonstrated that this species has pharmacological properties that make it a promising source of new antibacterial agents. Therefore, the present study aimed to evaluate the antibacterial and antibiotic-modulating activity of Baccharis coridifolia essential oil against multidrug-resistant (MDR) strains. The phytochemical analysis was carried out by gas chromatography coupled to Mass Spectroscopy (GC/MS), and realized the Minimum Inhibitory Concentation (MIC) and antibiotic-modulation from the microdilution method in 96-well plates. It was revealed the presence of germacrene D (23.7%), bicyclogermacrene (17.1%), and (E)-caryophyllene (8.4%) as major components. The minimum inhibitory concentration of essential oil against strains of Pseudomonas aeruginosa (512 µg/mL) and Staphylococcus aureus (128 µg/mL) demonstrated clinically relevant antibacterial activity. In addition, the combination of subinhibitory doses of the oil with conventional antibiotics showed synergism, indicating potentiation of the antibacterial effect. In conclusion, the essential oil of Baccharis coridifolia (EOBc) presented antibacterial and antibiotic-modulating activities that place this species as a source of molecules useful in the fight against bacterial resistance.