RESUMO

The chemical stability of 3-chloro-2-hydroxy-(3, 4-dimethyl-5-isoxazolyl)-1,4-naphthoquinon-4-imine (ClQ(1)), a new potential antimicrobial agent was analyzed at different pH values by first-derivative spectroscopy. The degradation of ClQ(1) followed a pseudo-first-order kinetics in aqueous media at different pH values. The interaction of antibiotics with respiratory chain of Staphylococcus aureus generates superoxide anion, an oxygen radical capable of producing damage to the bacteria. The performed assays have demonstrated that ClQ(1) presents higher activity and toxic oxidant generation at pH 5.0 than at pH 7.5. In addition, the antibacterial activity of other halogenated isoxazolylnaphthoquinones was also studied in different collection and clinical strains which presented the following decreasing activity, ClQ(1) > BrQ(1) > DClQ(1) whereas DBrQ(1) did not show inhibition properties. The antibacterial and stability properties evidenced by ClQ(1) are so important that must be taken into account when new alternative treatments against beta-lactamase-positive S. aureus strains are investigated.

Assuntos

RESUMO

Staphylococcus aureus was inhibited by exposure to 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (Q1). This compound was cleavaged in the presence of bacteria and an efflux of isoxazolamine was detected whereas in the S. aureus membrane and cytoplasm was observed an absorption band similar to that of the bencenoid ring. Non-viable bacteria showed intact Q1 intracellularly and in the membrane. Antistaphylococcus effect was associated to Q1 interaction with the respiratory chain, the oxidative metabolites were stimulated; there was cellular injury simultaneous to reduction of antibiotic molecule and efflux of isoxazolamine. The bacteria treated with Q1 increased its oxygen consumption and superoxide anion generation. Superoxide dismutase (SOD) production was stimulated, but it was principally extracellular in S. aureus. Escherichia coli, a species resistant to the antibiotic, did not reduce Q1 and showed lower superoxide anion generation; besides, there was an increase of intracellular SOD with extracellular decrease.

Assuntos

RESUMO

The 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (Q1) revealed good activity against Staphylococcus aureus. Q1 in contact with the bacteria experimented reduction evidenced by changes in its spectrum of absorption simultaneously with loss of colour. During the first 4 hours of incubation, oxygenation restored the original spectrum. Treatment with sodium borohydrure reduces irreversibly Q1. Redox-reaction "in vitro" was detected between Q1 and NADH in the presence of diaphorase. The environment of the probable site of action of Q1 was simulated using an artificial membrane system, instead of S. aureus membranes. Q1 interacts with lisophosphatidylcholine micelles following a cooperative binding model. The kinetics of Q1-reduction was increased by lipid micelles incorporated with the antibacterial compound.

Assuntos

RESUMO

The mechanism by which a new naphthoquinone derivative, the 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1, 4-naphthoquinone-4-imine (INQI-E) has antibacterial effect against Staphylococcus aureus was studied. The interaction of INQI-E with the bacteria was followed by absorption spectroscopy at 323 and 490 nm. The absorption band of INQI-E at 490 nm undergoes a hypochromic shift with a decrease of intensity. This effect was found to be reversible by oxygenation during the first hours of incubation. The participation of an oxidation-reduction process related to the respiratory chain was demonstrated by oxygen consumption. An increase in O2 uptake and inhibition of S. aureus growth was observed. Experiments with three inhibitors of the respiratory chain demonstrated that the pathway induced by INQI-E was antimycin-resistant and KCN- and salicylhydroxamic acid (SHAM)-sensitive, which suggests that INQI-E is capable of diverting the normal electron flow to an alternate superoxide-producing route. On the other hand, experiments with Tiron, a specific scavenger of superoxide, hindered the effect of INQI-E against S. aureus, indicating that the inhibitory growth effect of this quinone-imine is mainly due to the production of the cytotoxic superoxide radical.

Assuntos

RESUMO

The antibiotic activity of new synthetic isoxazolylnaphthoquinone imines was studied. Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922 were resistant to the four compounds studied (MIC > 128 micrograms ml-1), but Staphylococcus aureus ATCC 25923, ATCC 29213 and 30 clinical isolates of Staph. aureus were inhibited by 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (I). This compound diminished bloodstream infection of mice injected i.m. with Staph. aureus; septicaemia decayed significantly when I was applied at the beginning of the infection while when I was given 3 d after bacterial challenge, a significant protection was afforded. Bactericidal activity in serum increased during the 5 h after I was administered i.p. The acetyl derivative of I had a high MIC but when inoculated orally in mice decreased the Staph. aureus counts in circulation. This protection occurred only when the schedule of administration started close to the bacterial challenge. Antibiotic activity in vivo may be associated with in vitro effects.

Assuntos

Assuntos

Assuntos

RESUMO

The in vitro antibacterial activity of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl) 1,4 naphthoquinone-4-imine (I) and three of this derivatives against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis y Morganella morganii was investigated. From the four naphthoquinone-imine studied, compound I exhibited activity against S. aureus. This effect was observed even in oxygen atmosphere with 5% CO2 and in the presence of human albumin. The development of drug-resistant strains by serial passage in media with concentrations lower than the C.I.M. was determined in 31 strains of S. aureus from clinical material and one from collection. No significant differences in C.I.M. were observed.

Assuntos

RESUMO

The in vitro antibacterial activity of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl) 1,4 naphthoquinone-4-imine (I) and three of this derivatives against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis y Morganella morganii was investigated. From the four naphthoquinone-imine studied, compound I exhibited activity against S. aureus. This effect was observed even in oxygen atmosphere with 5

CO2 and in the presence of human albumin. The development of drug-resistant strains by serial passage in media with concentrations lower than the C.I.M. was determined in 31 strains of S. aureus from clinical material and one from collection. No significant differences in C.I.M. were observed.

RESUMO

The in vitro antibacterial activity of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl) 1,4 naphthoquinone-4-imine (I) and three of this derivatives against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis y Morganella morganii was investigated. From the four naphthoquinone-imine studied, compound I exhibited activity against S. aureus. This effect was observed even in oxygen atmosphere with 5

CO2 and in the presence of human albumin. The development of drug-resistant strains by serial passage in media with concentrations lower than the C.I.M. was determined in 31 strains of S. aureus from clinical material and one from collection. No significant differences in C.I.M. were observed.