In vitro evaluation of the antielastase activity of polycyclic β-lactams.
A series of bi- and tricyclic β-lactam compounds was synthesized and evaluated as inhibitors of cleavage of synthetic substrates in vitro by the serine proteases Human Leukocyte Elastase (HLE), Human Leukocyte Proteinase 3 (HLPR3) and Porcine Pancreatic Elastase (PPE). The obtained results have permitted us to describe a homobenzocarbacephem compound as HLE and HLPR3 inhibitor, to observe the positive effect that the styryl group exerts on the HLE inhibitory activity in polycyclic β-lactam compounds and to conclude that the hydroxyl function decreases the HLE inhibitory activity or rules it out completely.
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad de Salamanca, Plaza de los Caídos s/n, E-37008 Salamanca, Spain.
Laura M
LM
Monleón
Fernando
F
Díez-García
Héctor
H
Zamora
Josefa
J
Anaya
Manuel
M
Grande
Juana G
JG
de Diego
F David
FD
Rodríguez
D000818:Animals; D002511:Cephalosporins / Q000737:chemistry; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053146:Myeloblastin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D013552:Swine; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry*
D002511:Cephalosporins; D011480:Protease Inhibitors; D047090:beta-Lactams; C026739:carbacephems; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D053146:Myeloblastin