Mode of Action of Quindoxin and Substituted Quinoxaline-di- N -Oxides on Escherichia coli

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Abstract
The effect of quindoxin on the synthesis of deoxyribonucleic acid (DNA), ribonucleic acid, and protein in Escherichia coli KL 399 was examined under aerobic and anaerobic conditions. In the absence of oxygen the synthesis of DNA was completely inhibited by 10 ppm of quindoxin, whereas the syntheses of ribonucleic acid and protein were not affected. Quinoxalin-di- N -oxides (QdNO) induce degradation of DNA in both proliferating and non-proliferating cells. polA, recA, recB, recC, exrA , and uvrA mutants were more susceptible than the corresponding repair-proficient strains. All strains were more resistant in the presence of oxygen. Quindoxin was reduced to quinoxalin- N -oxide by intact E. coli cells or by a cell-free E. coli extract. Electron spin resonance measurements demonstrated the generation of free radicals during the reduction of quindoxin. Oxygen or deficiency of energy sources impaired the antibiotic activity and the reduction of QdNO. The QdNO reductase activity was demonstrated to be lower in QdNO-resistant mutants than in the susceptible parent strain. Based on these results it is concluded that an intermediate of reduction, probably a free radical, is responsible for the lethal effect of quindoxin. With three independent techniques no evidence has been found for binding of quindoxin to DNA.

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