Triterpenes and phytosterols as human leucocyte elastase inhibitors.
Ten triterpenes and phytosterols beta-amyrin, lupeol, lupeol acetate, ursolic acid, friedelin, canophyllol, 29-hydroxy-friedelan-3-one, beta-sitosterol, 3- O-beta- D-glucopyranosyl-beta-sitosterol, 3-O-(6'- O-palmitoyl)-beta-D-glucopyranosyl-beta-sitosterol, were evaluated as potential inhibitors of human leucocyte elastase (HLE). In this series, lupeol, ursolic acid and canophyllol showed marked HLE inhibitory activity with IC(50) values at 1.9 microM, 4.4 microM, and 2.5 microM, respectively. It appeared that HLE inhibition depended on the presence and the orientation of two reactive groups in the tested molecules, distant from 10-12 A, reacting with Arg-217 in S(4) -S(5) subsites of the extended substrate-binding domain of HLE, and S(3), respectively.
Mitaine-Offer
Anne-Claire
AC
Laboratoire de Pharmacognosie, Faculté de Pharmacie, Université de Reims Champagne-Ardenne, Reims, France. acoffer@u-bourgogne.fr
Hornebeck
William
W
Sauvain
Michel
M
Zèches-Hanrot
Monique
M
D029402:Bignoniaceae; D029911:Caesalpinia; D006801:Humans; D020128:Inhibitory Concentration 50; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D029586:Moraceae; D010840:Phytosterols / Q000008:administration & dosage / Q000494:pharmacology*; D008517:Phytotherapy; D010946:Plants, Medicinal; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D010840:Phytosterols; D014315:Triterpenes; D019272:Leukocyte Elastase