Derivatives of p-aminobenzoic acid and their action on the growth of bacteria
SummaryVarious derivatives of P.A.B. obtained by introduction of substituents in the benzene-nucleus have been examined for their action on the growth ofAerobacter aerogenes in a simple synthetic medium and ofDiplococcus pneumoniae in ascites-broth without peptone.The following results have been obtained:1.The 2-amino, 3-amino, 3-chloro, 3-bromo, 2-methyl, 3-methyl, and 2.3-dimethyl derivatives of P.A.B., and also 2-sulfanilamido-4-aminobenzoic acid have sulfonamide activity.2.The 2-hydroxy, 2-fluoro, and 2-nitro derivatives have an antisulfonamide activity similar to the activity of P.A.B., although weaker.3.The 3-hydroxy, 2-chloro, and 2-bromo derivatives show sulfonamide-activity in relatively high concentrations. In lower concentrations they act as anti-sulfonamides.4.The 3-nitro, 2.6-dimethyl, and 3.5-dimethyl derivatives, and methyl 2-acetamino-4-amino-benzoate are completely inactive. These results have been compared with those of other investigators and the causes of some contradictions have been elucidated.
Mechanism of Sulfonamide Action. III. Biological Action of Substituted p-Aminobenzoic Acids.∗
Summary The biological action of substituted p-aminobenzoic acids studied in this series of experiments is summarized in Table V. Substitutions on the ring of p-aminobenzoic acid resulted in compounds which were either inactive or had varying degrees of sulfonamide or antisulfonamide action. Although the compounds with sulfonamide action are relatively non-toxic, their value in systemic chemotherapy has not been demonstrated.
Pyridine-3-sulphon-(2-pyridyl)-amide; a Note on the Modelling of Chemotherapeutic Agents
THIS compound (I) was prepared for the following reason: pyridine-3-sulphonic acid and its amide were found to inhibit bacterial growth, apparently by interference with nicotinic acid metabolism1. Sulphanilamide appears to act as a therapeutic agent by interfering with the utilization of p-aminobenzoic acid by the invading organisms2, but the 2-aminopyridine derivative(M. &#38; B. 693) is in many cases more effective. Following a rule of thumb method common in chemotherapeutic research, the M. &#38; B. 693 analogue of pyridine-3-sulphonic acid, (I), was prepared and its inhibitory powers compared with those of the parent acid and amide by in vitro tests analogous to those previously described1,2. The compound was found less active than the simple acid and amide.