Mechanism of antibacterial and degradation behavior of a chlorinated isoxazolylnaphthoquinone.
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.
Bogdanov
P M
PM
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, Córdoba, 5000, Argentina.
Dabbene
V G
VG
Albesa
I
I
de Bertorello
M M
MM
Briñón
M C
MC
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002713:Chlorine; D004355:Drug Stability; D004579:Electron Transport / Q000187:drug effects; D016946:Gram-Negative Aerobic Rods and Cocci / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007555:Isoxazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013210:Staphylococcus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
C121800:3-chloro-2-hydroxy-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinon-4-imine; D000900:Anti-Bacterial Agents; D007555:Isoxazoles; D009285:Naphthoquinones; D013481:Superoxides; D002713:Chlorine