Antibacterial effect of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1, 4-naphthoquinone-4-imine on Staphylococcus aureus.
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.
Bogdanov
P
P
Departmento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Albesa
I
I
Sperandeo
N R
NR
Luna
C
C
de Bertorello
M M
MM
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000968:Antimycin A / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D007555:Isoxazoles / Q000008:administration & dosage / Q000494:pharmacology*; D009284:Naphthols / Q000008:administration & dosage / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011190:Potassium Cyanide / Q000494:pharmacology; D012457:Salicylamides / Q000494:pharmacology; D013053:Spectrophotometry; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D007555:Isoxazoles; D009284:Naphthols; D012457:Salicylamides; D000968:Antimycin A; C070800:2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone imine; C005703:salicylhydroxamic acid; D011190:Potassium Cyanide