Citation

Reboud-Ravaux MC, Boggetto ND, Doucet CE, de Rosny EH, Vergely IB, Thierry NM, Amour AJ. J. Pharm. Belg. 1996; 51(3): 161-164.

Copyright

(Copyright © 1996, Nationale Pharmaceutique)

DOI

unavailable

PMID

8778349

Abstract

The interaction of novel series of synthetic inhibitors with various serine proteases (leukocyte elastase, thrombin, cathepsin G, chymotrypsin, plasminogen activators and plasmin) and an aspartic protease (HIV-1 protease) were studied. Various aspects were analyzed: mechanism of action, structure-activity relationships, and in some cases, molecular modelling and biological evaluation. Functionalized cyclopeptides and N-aryl azetidin-2-ones behaved as suicide substrates acting specifically on trypsin-like proteases (thrombin or urokinase) and elastases, respectively. Novel hydrazinopeptides acted as reversible inhibitors of elastases. Coumarin derivatives inactivated very efficiently chymotrypsin-like proteases (k(inact)/K(I) = 760,000 M(-1).s(-1)). Inhibitors of HIV-1 protease acting either as inactivators or dimerization inhibitors are under investigation. The inhibitors described above are useful for elucidating the biological roles of the target enzymes and constitute potential drugs.

Language: fr

Keywords

Animals; Aspartic Acid Endopeptidases; Humans; Protease Inhibitors; Serine Proteinase Inhibitors