Biochemical Characterization of Actions of Chemotherapeutic Agents

Abstract

The bacteriostatic actions of sulphanilamide and pantoyltaurine have many characters in common, including those associated with their antagonism by compounds which are structurally related to the inhibitors and which are of natural occurrence. In the case of antagonism by p-aminobenzoate to the action of sulphanilamide, Woods (1940) and Fildes (1940) concluded that the interaction was by a competitive mechanism. A more quantitative demonstration of this was given by Wyss (1941); he, with later workers, based his analysis of the antagonism on equations which assumed equilibria between the reactants and some component of the micro-organisms. The equilibria implied that (in a sense to be discussed) the amount of free p-aminobenzoic acid in a system containing susceptible bacteria and a limited amount of the acid would increase on addition ofsulphanilamide; Fildes (1940) and Harris & Kohn (1941) anticipated such 'displacement'. Similar characters have been shown, and mechanisms assumed, for the antagonism by pantothenate to the antibacterial action of pantoyltaurine (Mcllwain, 1942, 1944). In neither case has the 'displacement' been directly observed, and the biological conditions under which it might occur, or the quantities of substances which it might involve, have not been specified. Although Green (1940) indicated that no considerable liberation of sulphonamide antagonists from Brucella abortus was caused by sulphanilamide, a displacement of paminobenzoic acid adsorbed on charcoal or a blocking of the adsorption, by sulphonamides, have been considered as models of the actions of the drugs by Hartmann & Druey (1943) and Eyster (1943). The possible displacement of p-aminobenzoate and pantothenate from microbial cells has now been examined. The method adopted in the case of pantothenate permitted observation of the release, from a small quantity of cells, of about 1/1000 of their pantothenate content. As it was not found possible by Feinstone, Williams & Florestano (1942) to correlate the absorption of sulphonamides by bacteria with their biological action (as was the case with arsenicals: Hawking, 1937, 1938), any observation of displacement would have additional significance as affording a possible connexion between the changed biological behaviour of susceptible organisms in the presence of the inhibitors and changes in their cell substance.

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Cite this paper

@inproceedings{McIlwain2005BiochemicalCO, title={Biochemical Characterization of Actions of Chemotherapeutic Agents}, author={Henry McIlwain}, year={2005} }