An "in vitro" system simulates in membranes the antibacterial mechanism postulated for the action of isoxazolylnaphtoquinoneimine in Staphylococcus aureus.
The 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4-imine (Q1) revealed good activity against Staphylococcus aureus. Q1 in contact with the bacteria experimented reduction evidenced by changes in its spectrum of absorption simultaneously with loss of colour. During the first 4 hours of incubation, oxygenation restored the original spectrum. Treatment with sodium borohydrure reduces irreversibly Q1. Redox-reaction "in vitro" was detected between Q1 and NADH in the presence of diaphorase. The environment of the probable site of action of Q1 was simulated using an artificial membrane system, instead of S. aureus membranes. Q1 interacts with lisophosphatidylcholine micelles following a cooperative binding model. The kinetics of Q1-reduction was increased by lipid micelles incorporated with the antibacterial compound.
Bogdanov
P
P
Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Gonzalez
M
M
Sperandeo
N R
NR
Fidelio
G
G
Albesa
I
I
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008055:Lipids; D008567:Membranes, Artificial; D008823:Micelles; D008826:Microbial Sensitivity Tests; D009243:NAD / Q000378:metabolism; D009284:Naphthols / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013054:Spectrophotometry, Atomic; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D007555:Isoxazoles; D008055:Lipids; D008567:Membranes, Artificial; D008823:Micelles; D009284:Naphthols; D009243:NAD; C070800:2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone imine; D008058:Dihydrolipoamide Dehydrogenase