title: Triterpenes and phytosterols as human leucocyte elastase inhibitors.
abstract: 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.
authors.affiliation: Laboratoire de Pharmacognosie, Faculté de Pharmacie, Université de Reims Champagne-Ardenne, Reims, France. acoffer@u-bourgogne.fr
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Mitaine-Offer
authors.forename: William
authors.initials: W
authors.lastname: Hornebeck
authors.forename: Michel
authors.initials: M
authors.lastname: Sauvain
authors.forename: Monique
authors.initials: M
authors.lastname: Zèches-Hanrot
mesh_terms: 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*
chemical_list: D010840:Phytosterols; D014315:Triterpenes; D019272:Leukocyte Elastase