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 cat hepsin G. Most of the compounds were found to be efficient and time-de pendent inhibitors of elastase. Inactivated elastase was found to rega in its activity almost fully after 24 h (80-90 % activity) and the hal f-lives of reactivation ranged between 12-15 h. Addition of hydroxylam ine 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.