RESUMO
The biological activity of 5-amino-8-hydroxy-1,4-naphthoquinone (ANQ) on Staphylococcus aureus was investigated in comparison with the unsubstituted 1,4-naphthoquinone (NQ). Complete inhibition of microbial growth was observed with ANQ and NQ at 50 and 10 microg/mL, respectively. The antibacterial effect of naphthoquinones decreased in the presence of sodium ascorbate, but the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron) was able to protect S. aureus only from the harmful effect of ANQ. Naphthoquinones blocked oxygen uptake and induced cyanide-insensitive oxygen consumption. When combining rotenone or salicylhydroxamic acid with ANQ or NQ, a slight decrease in respiratory activity was observed. Assays in the presence of naphthoquinones induced an increase of lipid peroxidation in S. aureus, as determined by thiobarbituric acid reactive substances. These results showed that 1,4-naphthoquinones effectively act as electron acceptors and induce an increase in reactive oxygen species that are toxic to S. aureus cells.
Assuntos
Naftoquinonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
AIMS: The objective of this study was to investigate the interactions between 5-amino-8-hydroxy-1,4-naphthoquinone (ANQ) and Staphylococcus aureus. METHODS AND RESULTS: The compound ANQ display antimicrobial activity against S. aureus. During incubation with 50 microg ml(-1) of ANQ, an unusual reduction reaction takes place and leads to the isolation of 2,3-dihydro-5-amino-8-hydroxy-1,4-naphthoquinone (ANQ-H(2)), fully characterized by means of (13)C-NMR and (1)H-NMR, plus infrared, UV-visible and mass spectroscopy. Oxygen uptake by S. aureus cells was inhibited by ANQ, but in a significantly minor extent by ANQ-H(2). CONCLUSIONS: The ability of S. aureus to reduce the double bond at C2-C3 of the ANQ is a unusual behaviour for biological transformation of naphthoquinones. SIGNIFICANCE AND IMPACT OF THE STUDY: This uncommon reaction may provide valuable understanding of the S. aureus regarding to the antimicrobial effect and the acquisition of resistance to naphthoquinones.
Assuntos
Naftoquinonas/metabolismo , Staphylococcus aureus/metabolismo , OxirreduçãoRESUMO
The antibacterial activity of a series of 1,4-naphthoquinones was demonstrated. Disk diffusion tests were carried out against several Gram-positive and Gram-negative bacteria. The compound 5-amino-8-hydroxy-1,4-naphthoquinone was the most effective, presenting inhibition zones measuring 20 mm against staphylococci, streptococci and bacilli at 50 microg/ml. Methicillin-resistant Staphylococcus aureus and several clinical isolates of this bacterium were also inhibited. Naphthazarin, 5-acetamido-8-hydroxy-1,4-naphthoquinone, and 2,3-diamino-1,4-naphthoquinone were the next most active compounds. The minimal inhibitory concentration of the active compounds was determined against S. aureus, ranging from 30 to 125 microg/ml. All compounds presented a minimal bactericidal concentration higher than 500 microg/ml, indicating that their effect was bacteriostatic. The EC50, defined as the drug concentration that produces 50% of maximal effect, was 8 microg/ml for 5-amino-8-hydroxy-1,4-naphthoquinone against S. aureus, S. intermedius, and S. epidermidis. These results indicate an effective in vitro activity of 5-amino-8-hydroxy-1,4-naphthoquinone and encourage further studies for its application in antibiotic therapy.
Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Naftoquinonas/farmacologia , Animais , Antibacterianos/química , Resistência Microbiana a Medicamentos , Listeria/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Naftoquinonas/química , Ovinos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Streptococcus/efeitos dos fármacosRESUMO
The antibacterial activity of a series of 1,4-naphthoquinones was demonstrated. Disk diffusion tests were carried out against several Gram-positive and Gram-negative bacteria. The compound 5-amino-8-hydroxy-1,4-naphthoquinone was the most effective, presenting inhibition zones measuring 20 mm against staphylococci, streptococci and bacilli at 50 æg/ml. Methicillin-resistant Staphylococcus aureus and several clinical isolates of this bacterium were also inhibited. Naphthazarin, 5-acetamido-8-hydroxy-1,4-naphthoquinone, and 2,3-diamino-1,4-naphthoquinone were the next most active compounds. The minimal inhibitory concentration of the active compounds was determined against S. aureus, ranging from 30 to 125 æg/ml. All compounds presented a minimal bactericidal concentration higher than 500 æg/ml, indicating that their effect was bacteriostatic. The EC50, defined as the drug concentration that produces 50 percent of maximal effect, was 8 æg/ml for 5-amino-8-hydroxy-1,4-naphthoquinone against S. aureus, S. intermedius, and S. epidermidis. These results indicate an effective in vitro activity of 5-amino-8-hydroxy-1,4-naphthoquinone and encourage further studies for its application in antibiotic therapy
Assuntos
Animais , Anti-Infecciosos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Técnicas In Vitro , Naftoquinonas , Anti-Infecciosos , Resistência Microbiana a Medicamentos , Listeria , Testes de Sensibilidade Microbiana , Naftoquinonas , Ovinos , Staphylococcus aureus , StreptococcusRESUMO
The phenomenon of electrophoresis in free solution has been studied theoretically down to the molecular level for decades. In addition, intermolecular photo-induced proton transfer reactions, which occur in a wide class of molecules (phenols and aminoarenes) as well as proteins (green fluorescent protein), were also studied extensively. However, the study of the effect of light-induced electrophoretic mobility changes of the analytes in electrophoresis was begun only recently. In the present work, capillary zone electrophoresis was chosen as the environment to measure the magnitude of these electrophoretic mobility shifts induced by light. Background electrolytes (running electrolytes) with high refractive indices were developed, allowing the capillary to work like an optical fiber. The experimental conditions for obtaining stable coupling and guided laser light along the liquid core are discussed. Experimental evidence of band compression is observed, leading to a solitary wave behavior of the analyte band (2-naphthol). These solitary waves result from competition between thermal diffusion (dispersion mechanism) and a nonlinear (band compression) effect due to the combined electrophoresis phenomenon and absorption of guided light by the molecules of the band (which are subjected to a "reversible intermolecular proton transfer reaction" as one of their decay routes). The possibilities of applying this effect to different methods and techniques are also discussed.
Assuntos
Eletroforese Capilar/métodos , Soluções Tampão , Luz , NaftóisRESUMO
For development of new cardiotonic agents a series of 5-aryl-3,4-dihydropyridin-2(1H)-ones, related to amrinone have been prepared from methylquinolines, 2-arylacetic acid or 3-arylethanones by direct aminomethylenation and subsequent condensation-cyclization with malonamide and cyanacetamide in classic basic media or phase-transfer catalysis, in good to excellent yields. Preliminary pharmacological assays have shown that these compounds, especially 5h and 5i, have a remarkable cardiotonic effect and present a selective inhibition of PDE-III/PDE-I isolated from cat heart.