title: 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 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.
mesh_terms: D062365:Aminobenzoates; D003622:Dapsone / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D011621:Pteridines; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*; D014166:Transferases / Q000037:antagonists & inhibitors*
chemical_list: D062365:Aminobenzoates; D011621:Pteridines; D013449:Sulfonamides; D013450:Sulfones; D003622:Dapsone; D014166:Transferases