Effect of Prontosil and Prontylin on Metabolism of Bacteria

Abstract

Donagk discovered 1 that certain sulfonamide compounds are good therapeutic agents against certain bacterial infections, a discovery confirmed by a number of investigators; but the mechanism of this action has not yet been explained.

The bactericidal properties of the reduced sulfonamide compounds, as shown by the inhibition of bacterial growth in cultures, have been reported (Fourneau and coworkers, 2 Colebrook, Buttle, and O'Meara, 3 Long and Bliss 4 ). Since the oxidized forms (Prontosil, Prontosil soluble) were found devoid of bactericidal properties, it has been assumed that these drugs become active by their reduction in the animal body (Bliss and Long 5 ).

The effect of Prontosil (4-sulfonamide, 2,4'-diamino azobenzol) and of Prontylin∗ (p-amino benzene sulfonamide) on the metabolism of hemolytic streptococci, B. coli, B. Friedlander, and gonococci was studied in an endeavor to clarify the mechanism of their chemotherapeutic properties. The experiments were performed at 38° with the usual Warburg-Barcroft respiration apparatus. The bacteria were washed in 0.9% NaCl and suspended in the same salt solution, which was buffered to pH 6.87 by addition of phosphates. The concentration of the drugs was 0.01 M per liter; that of metabolites, 0.008 M per liter. Each experiment was done in quadruplicate, the maximum error being 5%. Prontosil had no effect on the metabolism of these bacteria. Prontylin had a slight inhibiting effect on the oxidation of glucose by hemolytic streptococci, and on the oxidation of glucose and lactate by B. Friedlander (Table 1).

Prontosil, which is irreversibly reduced by Na₂S₂O₄, has an apparent reduction potential of +0.100 volt ±0.01 at pH 6.93. As there exist in the animal body a number of oxidation-reduction systems of more negative potential, Prontosil might be easily reduced in the body.