Inhibition of dihydropteroate synthetase from Escherichia coli by sulfones and sulfonamides.

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 x 10(-5) M) and the monosubstituted derivatives 4-amino-4'-formamidodiphenylsulfone (I(50) = 5.8 x 10(-5) M) and 4-amino-4'-acetamidodiphenylsulfone (I(50) = 5.2 x 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 x 10(-6) M) and sulfadiazine (K(I) = 2.5 x 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.