Efficient inhibition of human leukocyte elastase and cathepsin G by saccharin derivatives.
A series of saccharin derivatives I has been synthesized and evaluated for their inhibitory activity toward human leukocyte elastase and cathepsin G. Most of the compounds were found to be efficient and time-dependent inhibitors of elastase. Inactivated elastase was found to regain its activity almost fully after 24 h (80-90% activity) and the half-lives of reactivation ranged between 12-15 h. Addition of hydroxylamine to fully-inactivated enzyme led to rapid and complete recovery of enzymatic activity. A tentative mechanism of action is proposed on the basis of biochemical and model studies.
Groutas
W C
WC
Department of Chemistry, Wichita State University, Kansas 67260.
Houser-Archield
N
N
Chong
L S
LS
Venkataraman
R
R
Epp
J B
JB
Huang
H
H
McClenahan
J J
JJ
D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D006801:Humans; D019272:Leukocyte Elastase; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D012439:Saccharin / Q000031:analogs & derivatives*; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship
D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D012439:Saccharin