Design, synthesis, and in vitro inhibitory activity toward human leukocyte elastase, cathepsin G, and proteinase 3 of saccharin-derived sulfones and congeners.
The inhibitory activity toward human leukocyte elastase (HLE), cathepsin G (Cat G), and proteinase 3 (PR 3) of a series of saccharin derivatives having a sulfinate leaving group was investigated. The results of this study revealed that (a) inhibitory activity is dependent on the nature and pKa of the leaving group, and (b) the synthesized saccharin derivatives exhibit selective inhibition toward HLE and PR 3, with low or no activity toward cathepsin G. The results of exploratory biochemical, HPLC and high-field 13C NMR studies are also described.
Groutas
W C
WC
Department of Chemistry, Wichita State University, KS 67260-0051, USA.
Epp
J B
JB
Venkataraman
R
R
Kuang
R
R
Truong
T M
TM
McClenahan
J J
JJ
Prakash
O
O
D001324:Autoantigens / Q000276:immunology; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D053146:Myeloblastin; D011480:Protease Inhibitors / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000037:antagonists & inhibitors*
D001324:Autoantigens; D011480:Protease Inhibitors; D013450:Sulfones; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D053146:Myeloblastin