Inhibition of bacterial DNA synthesis

Nalidixic acid and its analogues act by inhibition of bacterial DNA synthesis by inhibiting a bacterial DNA gyrase classified as a type II topoisomerase.(7.8.9.10) Resistance and cross resistance are seen with nalidixic acid and the fluoroquinolones. It seems to be related to decreased cellular permeability and has been considered plasmid independent. ( ,5,11,12) More recently, reports have appeared of genes carrying the resistance traits normally found on plasmids. (13,1 )... 

Oxolonic acid is in vitro more efficient than nalidixic acid. The therapeutic mechanism is in this case too thought to be inhibition of bacterial DNA synthesis. The optimal action is in the range of pH 6.5-8. The half-life in serum is 2 /2-3 h. After oral administration of 4 x 240 mg oxolonic acid to human subjects, serum concentrations of 1.8 pg/ml and average 24-h-urine concentrations of 40 pg/ml are reached. 

G—C rich regions of DNA, in contrast to mercury, and separation founded on this basis can also be achieved [103]. Again a crystal structure of l-(methylcytosine)silver(I) nitrate may serve as model for the DNA interaction [104]. This complex is also of interest because of its dimeric nature. The proposed inhibition of bacterial DNA synthesis by the Ag" ion (Chapter 9) is relevant here, although no attempts appear to have been made to correlate cytotoxicity with modes of binding. 

H. S. Rosenkranz, A. J. Garro, J. A. Levy, and H. S. Carr, Studies with hydroxyurea. I. The reversible inhibition of bacterial DNA synthesis and the effect of hydroxyurea on the bactericidal action of streptomycin, Biochim. Biophys. Acta 114, 501-515 (1966). 

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See also in sourсe #XX -- [ ]

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