Cytotoxic diterpenoids from the roots of Euphorbia ebracteolata

Three new diterpenoids, yuexiandajisu D (1), E (2) and F were isolated from the roots of Euphorbia ebracteolata, along with eight known diterpenoids, jolkinolide B (4), jolkinolide A, ent-11 alpha-hydroxyabieta-8(14),13(15)-dien-16,12 alpha-olide (6), ent-(13S)hydroxyatis-16-ene-3,14-dione, ent-3 beta,(13S)-diliydroxyatis-16-en-14-one, ent-3-oxokaurane-16 alpha,17-diol, ent-16 alpha,17-dihydroxyatisan-3-one and ent-atisane-3 beta,16 alpha,17-triol. The structures of all compounds were deduced using spectroscopic methods and confirmed for 1 and 2 by single-crystal X-ray diffraction. A biogenetic pathway for the formation of 1 and 2 is proposed briefly. Cytotoxic activities were evaluated against ANA-1, B 16 and Jurkat tumor cells. Jolkinolide B (4) displayed modest activity on ANA-1, B 16 and Jurkat tumor cells with IC50 values 4.46 x 10(-2), 4.48 x 10(-2), 6.47 x 10(-2) mu M, and ent-11 alpha-hydroxyabieta-8(14), 13(15)-dien-16,12 alpha-olide (6) showed significant activity against ANA-1 and Jurkat cells with IC50 values 7.12 x 10(-3) and 1.79 x 10(-2) mu M. Compound 1 was found to be slightly active against ANA-1 cells with an IC50 value 2.88 x 10(-1) mu M. Structure-activity relationships of isolated compounds are also discussed.