Sesquiterpenoids from Euphorbia esula L.

Six undescribed sesquiterpene esters, euphoresulins A-F, along with fourteen known daucane analogues were isolated from the aerial parts of Euphorbia esula growing in Uzbekistan. Their structures were determined on the basis of extensive spectroscopic analyses, with absolute configurations established by comparison of experimental and calculated ECD data, in addition to single-crystal X-ray diffraction crystallography. Euphoresulins A-F (1-6) presented sesquiterpene ester types of daucane for euphoresulins A-D (1-4) and aromadendrane for euphoresulins E-F (5-6). Compounds 7-20 were firstly isolated from the genus Euphorbia, wherein compound 7 was naturally unprecedented. Bioactivity assays revealed that three compounds (3, 9 and 10) carrying 9-keto group and 6-acyloxy residue of trisubstituted benzoyloxy moiety demonstrated anti-inflammatory effects by inhibiting the release of NO in LPS-induced RAW 264.7 macrophages, with IC values ranging from 22.49 ± 0.21 to 30.31 ± 1.19 μM. Additionally, five esters (3, 9, 11, 14 and 18) bearing Δ, Δ or 8β-OH, and 6-benzoyloxy groups with versatile substitution patterns displayed certain cytotoxic activities against HeLa, HT-29 and MCF-7 cell lines, representing IC values of 14.71 ± 0.75, 15.30 ± 0.75 and 26.36 ± 1.84 μM, respectively for compound 18.