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Inhibition of the Synthesis of Deoxyribonucleic Acid in Bacteria by 6-(p-Hydroxyphenylazo)-2,4-dihydroxypyrimidine

I. METABOLIC STUDIES IN STREPTOCOCCUS FECALIS

From the ¹ From the Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

6-(p-Hydroxyphenylazo)-2,4-dihydroxypyrimidine, a microbial inhibitor with selective toxicity for gram-positive bacteria, is bactericidal for growing cultures of Streptococcus fecalis at concentrations greater than 1.0 µM.

This phenylazopyrimidine specifically and completely inhibits the synthesis of deoxyribonucleic acid and has no apparent effects on major areas of intermediary metabolism or on the gross synthesis of lipid, ribonucleic acid, protein, and cell wall material. The inhibition of synthesis of DNA is not associated with an increased degradation of the DNA in cells to acid-soluble forms, and is completely reversed by removal of the drug from inhibited cultures. Since neither the formation of the essential deoxyribonucleoside triphosphate precursors of DNA nor the processes responsible for initiation of synthesis of DNA are inhibited, the primary locus of action is believed to be the polymerization reaction that results in the formation of DNA.

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