THE ANTIBACTERIAL ACTION OF DERIVATIVES AND ANALOGUES OF p-AMINOBENZOIC ACID

The bacteriostasis induced by the sulfonamide drugs is reversed by p-aminobenxoic acid (PAB) in appropriate concentrations (1). It is now well established that PAB is a normal constituent of cells (2) and that the bacteriostatic effects of the sulfonamides are explicable in terms of their structural similarity to PAB (3). The precise rble of PAB in cellular metabolism has yet to be clarified but whether it functions as a substrate as some investigators postulate (4), or more likely as a prosthetic group; clearly it must be involved in some reaction which is vital to the growth of many microorganisms. The sulfonamides, presumably by competing with PAB for a part in this key reaction, are able thereby to disrupt the economy of certain growing cells. Assuming that PAB is the molecule to be imitated, it follows that there must be compounds other than the sulfonamides which can compete with PAB. Thus, for example, sulfur-free compounds related in structure to PAB might be expected to produce bacteriostatic effects comparable to those of the sulfonamides. When the chemotherapeutic possibilities of derivatives and analogues of PAB were investigated, two objectives were in mind: (1) to develop another line of evidence in support of the thesis that the resemblance of the sulfonamides to PAB is the basis of their bacteriostatic properties and (2) to determine whether the bacteriostatic potencies reached by sulfonamides could be duplicated in other molecular configurations and whether the toxic properties which accompany the bacteriostatic effects of the sulfonamides would apply as well to other such bacteriostatic compounds. When the present investigation was begun, it had been reported that p-nitrobeneoic acid arrested quite strongly the growth of certain bacteria (5). Subsequently, Hirsch (6) showed that p-aminobenzamide also possessed bacteriostatic properties. While the work here described was in progress, Auhagen (7) and Kuhn and coworkers (8) reported varying degrees of antibacterial action for several sulfur-free compounds related