Abstract
Growth inhibition of E. coli cell culture has been determined for a series of 4-substituted-N'-phenylsulfonamides tested in the presence and absence of synergistic concentrations of trimethoprim. Quantitative structure-activity relationships, established by regression analysis, exhibit an identical dependence of bacterial growth inhibition on sulfonamide pKa irrespective of the presence or absence of trimethoprim. Examination of a small series of benzylpyrimidines in the presence or absence of 4-dimethylamino-N1-phenylsulfanilamide gave similar results. Since the presence of a synergistic agent affords no change in structure-activity relationships, it is concluded that no direct interaction between sulfonamides and benzylpyrimidines occurs and that the synergism observed is solely the result of the kinetic consequences of sequential blockade of the folate biosynthetic pathway.