title: Inactivation of human neutrophil elastase by 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamides.
abstract: The interaction of a series of 1,2,5-thiadiazolidin-3-one 1,1 dioxide-based sulfonamides with neutrophil-derived serine proteases was investigated. The nature of the amino acid component, believed to be oriented toward the S' subsites, had a profound effect on enzyme selectivity. This series of compounds were found to be potent, time-dependent inhibitors of human neutrophil elastase (HNE) and were devoid of any inhibitory activity toward neutrophil proteinase 3 (PR 3) and cathepsin G (Cat G). The results of these studies demonstrate that exploitation of differences in the S' subsites of HNE and PR 3 can lead to highly selective inhibitors of HNE.
authors.affiliation: Department of Chemistry, Wichita State University, Wichita, KS 67260, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Yang
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Dou
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Alliston
authors.forename: William C
authors.initials: WC
authors.lastname: Groutas
mesh_terms: D000465:Algorithms; D000818:Animals; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D053146:Myeloblastin / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D013830:Thiadiazoles; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D053146:Myeloblastin