New immunosuppressive cyclomyrsinol diterpenes from Euphorbia kopetdaghi Prokh

Aceton?:?chloroform (1?:?2) extracts of the aerial parts of Euphorbia kopetdaghi Prokh. (Euphorbiaceae) were investigated for its diterpenoids and afforded three new five-membered ring, pentacyclic myrisinane polyester comprised of 3,5,10-O-triacetyl-8-O-isobutanoyl-14-O-benzoylcyclomyrsinol (1), 3,5,10,14-O-tetraacetyl-8-O-(2'-methyl butanoyl)-cyclomyrsinol (2) and 3,5,10,14-O-tetracetyl-8-O-isobutanoylcyclomyrsinol (3). The structures were elucidated based on 13C- and 1H-NMR as well as 2D-NMR, IR and different MS spectra and the immunomodulation activity for compound 1 was evaluated through lymphocyte proliferation assay, IL-2 assay, oxidative burst of phagocytic leukocytes and through their cytotoxicity on two cell lines. Compound 1 showed significant suppressive activity against phytohemagglutinin-activated T-cell proliferation with an IC50 of 1.83 mu g?mL-1, IL-2 suppressive activity with an IC50 of 19.0 mu g mL-1 and oxidative burst suppressive activity with an IC50 of 1.6 mu g?mL-1 and ignorable cytotoxic effect on the CC-1 rat hepatocyte and 3T3-L1 mouse fibroblast cell-lines.