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 isoxazolyl-naphthoquinones 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. (C) 1999 Academic Press.