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 wa s analyzed at different pH values by first-derivative spectroscopy. The deg radation of ClQ(1) followed a pseudo-first-order kinetics in aqueous media at different pH values. The interaction of antibiotics with respiratory cha in of Staphylococcus aureus generates superoxide anion, an oxygen radical c apable of producing damage to the bacteria. The performed assays have demon strated that ClQ(1) presents higher activity and toxic oxidant generation a t pH 5.0 than at pH 7.5. In addition, the antibacterial activity of other h alogenated isoxazolyl-naphthoquinones was also studied in different collect ion and clinical strains which presented the following decreasing activity, ClQ(1) > BrQ(1) > DClQ(1) whereas DBrQ(1) did not show inhibition properti es. The antibacterial and stability properties evidenced by ClQ(1) are so i mportant that must be taken into account when new alternative treatments ag ainst beta-lactamase-positive S. aureus strains are investigated. (C) 1999 Academic Press.