Inhibition of Dihydropteroate Synthetase from Escherichia coli by Sulfones and Sulfonamides

Abstract

The inhibitory action of various diphenylsulfones and sulfonamides on dihydropteroate synthetase partially purified from Escherichia coli was examined. 4,4′-Diaminodiphenylsulfone (DDS; I 50 = 2 × 10 −5 M) and the monosubstituted derivatives 4-amino-4′-formamidodiphenylsulfone (I 50 = 5.8 × 10 −5 M) and 4-amino-4′-acetamidodiphenylsulfone (I 50 = 5.2 × 10 −5 M) were effective inhibitors of dihydropteroate synthetase activity. Disubstitution of the arylamine groups of DDS (4,4′-diformamidodiphenylsulfone and 4,4′-diacetamidodiphenylsulfone) resulted in complete loss of inhibitory activity. Both DDS ( K I = 5.9 × 10 −6 M) and sulfadiazine ( K I = 2.5 × 10 −6 M) were found to be competitive inhibitors of dihydropteroate synthetase. These findings are discussed in regard to the Bell and Roblin theory of structure-activity relationships for p -aminobenzoic acid antagonists.