ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chlorine , Isoxazoles/pharmacology , Naphthoquinones/pharmacology , Staphylococcus/drug effects , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/metabolism , Drug Stability , Electron Transport/drug effects , Gram-Negative Aerobic Rods and Cocci/drug effects , Hydrogen-Ion Concentration , Hydrolysis , Isoxazoles/chemistry , Isoxazoles/metabolism , Microbial Sensitivity Tests , Naphthoquinones/chemistry , Naphthoquinones/metabolism , Structure-Activity Relationship , Superoxides/metabolismABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Isoxazoles/metabolism , Isoxazoles/pharmacology , Naphthols/metabolism , Naphthols/pharmacology , Staphylococcus aureus/drug effects , Staphylococcus aureus/metabolism , Drug Resistance, Microbial , Escherichia coli/metabolism , Oxidative Stress/drug effects , Oxygen Consumption/drug effects , Spectrometry, Fluorescence , Spectrophotometry , Superoxide Dismutase/biosynthesis , Superoxides/metabolismABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Naphthoquinones/pharmacology , Microbial Sensitivity TestsABSTRACT
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.
ABSTRACT
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.
