Sesquiterpene coumarins from Ferula szowitsiana and in vitro antileishmanial activity of 7-prenyloxycoumarins against promastigotes

Two new sesquiterpene coumarins, named szowitsiacoumarin A (1) and szowitsiacoumarin B (2), and a phenylpropanoid derivative, 2-epihelmanticine (3), together with nine known compounds, auraptene (4), umbelliprenin (5), galbanic acid (6), methyl galbanate (7), farnesiferol B (8), farnesiferol C (9), persicasulfide A (10), beta-sitosterol and stigmasterol were isolated from the roots of Ferula szoivitsiana. The structures of these compounds were elucidated by extensive spectroscopic methods including 1D-(H-1 and C-13) and 2D-NMR experiments (DQF-COSY, HSQC, HMBC, and ROESY) as well as HR-MALDI-MS analysis. Since the configuration of 2-epihelinanticine was previously only partly determined, a relative configurational analysis of its four stereocenters was carried out on the basis of the recently reported J-based method. The inhibiting activity of prenylated coumarins, auraptene (4) and umbelliprenin (5), in addition to galbanic acid (6), as major component, and of the Me2CO extract of Ferula szowitsiana (Apiaceae) roots has been evaluated against promastigotes of Leishmania major. Umbelliprenin and auraptene showed significant activity with IC50 values of 4.9 mu g/ml (13.3 mu M) and 5.1 mu g/ml (17.1 mu M) after 48 h incubation, respectively. (c) 2006 Elsevier Ltd. All rights reserved.