Inhibition of Dihydropteroate Synthetase from Escherichia coli by Sulfones and Sulfonamides

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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.