title: Quantitative structure-activity relationships in dihydropteroate synthase inhibition by multisubstituted sulfones. Design and synthesis of some new derivatives with improved potency.
abstract: On the bases of the linear correlation existing for a training set of homomultisubstituted 4-aminodiphenyl sulfones between the computed (INDO) electronic net charges of the SO2 group and the enzymic inhibition data on dihydropteroate synthase from Escherichia coli, seven new heteromultisubstituted derivatives were designed, synthesized, and tested for their inhibition potencies. These compounds were found to be from 5-11 times more effective than 4,4'-diaminodiphenyl sulfone. The implications of the results in the drug design and in the model for the enzyme-inhibitors interaction are discussed.
authors.affiliation: Dipartimento di Chimica, Università di Modena, Italy.
authors.forename: P G
authors.initials: PG
authors.lastname: De Benedetti
authors.forename: D
authors.initials: D
authors.lastname: Iarossi
authors.forename: U
authors.initials: U
authors.lastname: Folli
authors.forename: C
authors.initials: C
authors.lastname: Frassineti
authors.forename: M C
authors.initials: MC
authors.lastname: Menziani
authors.forename: C
authors.initials: C
authors.lastname: Cennamo
mesh_terms: D004094:Dihydropteroate Synthase / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004926:Escherichia coli / Q000201:enzymology; D007202:Indicators and Reagents; D007700:Kinetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology; D014166:Transferases / Q000037:antagonists & inhibitors*
chemical_list: D007202:Indicators and Reagents; D013450:Sulfones; D014166:Transferases; D004094:Dihydropteroate Synthase