Triterpenes and phytosterols as human leucocyte elastase inhibitors

Ten triterpenes and phytosterols β-amyrin, lupeol, lupeol acetate, ursolic acid, friedelin, canophyllol, 29-hydroxy-friedelan-3-one, β-sitosterol, 3-O-β-D-glucopyranosyl-β-sitosterol, 3-O-(6′- O-palmitoyl)-β-D-glucopyranosyl-β-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 IC₅₀ values at 1.9 μM, 4.4 μM, and 2.5 μM, 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 Å, reacting with Arg-217 in S₄-S₅ subsites of the extended substrate-binding domain of HLE, and S3, respectively.