Chemotherapy of P-aminobenzenesulphonamide and related compounds

Abstract

1. From the 20 compounds tested for their chemotherapeutic action against mice infected with the haemolytic streptococcus, p- aminobenzenesulphon amide, M. & B. 693, (2- sulphanilylaminopyridine), 3- nitro -4- hydroxybenzenesulphonamide, 3- nitro -4- aminobenzenesulphonamide, 1: 4di(aminobenzenesulphon yl)piperazine and 1:4 diXacetylaminobenzenesulphonyl)piperazine showed definite activity. Of these 6 compounds, p- aminobenzenesulphonamide and 2- sulphanilylaminopyridine are already known to have antistreptococcal properties while 3- nitro -4- aminobenzenesulphonamide has been reported inactive. Investigations in the curative properties of the two piperazine derivatives, and of 3- nitro -4- hydroxybenzenesulphonamide have not been before reported.

2. Against a pneumococcal infection in mice p- aminobenzenesulphonamide had a slight death delaying effect, but the other 12 compounds examined' were inactive.

3. Using the staphylococcus as the infecting organism, diacetyldiaminodiphenylsulphide and 1 :4 di( acetylaminosulphonyl)piperazine had a protective action on the infected mice, while M. & B. 693 (2- sulphanilylaminopyridine) delayed death in the animals injected with the staphylococcus and fed with this compound.

4. No protective power could be demonstrated¡ with any of the 20 compounds against mice infected with Bacillus Aertrycke.

5. With some of the compounds a bactericidal effect was evident in vitro against the streptococcus and the pneumococcus, but against the staphylococcus and Bacillus Aertrycke there was little effect from any of the compounds. The results of the in vitro experiments do not run parallel to those obtained in the animal experiments, thus the effect in the animal body must be other than a simple bactericidal one.

6. The results are against the suggestion that the special conditions of animal tissue in respect of pH and Eh might modify the bactericidal action observed in the in vitro results.

7. No evidence could be obtained, from attempts to oxidise sulphanilamide by atmospheric oxygen in presence of enzymes or of manganese salts, that a highly active oxidation product could be formed.

8. The bearing of these results on the mechanism of the action of sulphanilamide is discussed.

INCLUDES INSERTS: The Use of Compounds Related to ρ-Aminobenzenesulphonamide in The Treatment of Certain Infections in Mice. [FROM THE BIOCHEMICAL JOURNAL, Vol. XXXII, No. 10, pp. 1770 -1774, 1938] • THE CHEMOTHERAPY OF TYPHOID AND SOME OTHER NON-STREPTOCOCCAL INFECTIONS IN MICE BY G. A. H. BUTTLE, H. J. PARISH, MORAG McLEOD and DORA STEPHENSON. Reprinted from THE LANCET, March 20th, 1937, p. 681