Cytotoxic Diterpenoids from the Roots of Euphorbia ebracteolata

Abstract

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-11α-hydroxyabieta-8(14),13(15)-dien-16,12α-olide (6), ent-(13S)-hydroxyatis-16-ene-3,14-dione, ent-3β,(13S)-dihydroxyatis-16-en-14-one, ent-3-oxokaurane-16α,17-diol, ent-16α,17-dihydroxyatisan-3-one and ent-atisane-3β,16α,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 × 10 ^{- 2}, 4.48 × 10 ^{- 2}, 6.47 × 10 ^{- 2} μM, and ent-11α-hydroxyabieta-8(14), 13(15)-dien-16,12α-olide (6) showed significant activity against ANA-1 and Jurkat cells with IC₅₀ values 7.12 × 10 ^{- 3} and 1.79 × 10 ^{- 2} μM. Compound 1 was found to be slightly active against ANA-1 cells with an IC₅₀ value 2.88 × 10 ^{- 1} μM. Structure-activity relationships of isolated compounds are also discussed.

Key words

Euphorbiaceae - Euphorbia ebracteolata - yuexiandajisus D - F - diterpenoids - cytotoxic activity

References

• 1 Jiangsu College of New M edicine. A Dictionary of the Traditional Chinese Medicines. Shanghai Science and Technology Press Shanghai; 1986: p 1898
• 2 Wang W X, Ding X B. Studies on diterpenoids from the roots of Euphorbia ebracteolata .  Acta Pharmaceutica Sinica. 1998;  33 128-31
• 3 Xu Z H, Sun J, Xu R S, Qin G W. Casbane diterpenoids from Euphorbia ebracteolata .  Phytochemistry. 1998;  49 149-51
• 4 Xu Z H, Qin G W, Xu R S. An isopimarane diterpene from Euphorbia ebracteolata Hayata.  Journal of Asian Natural Products Research. 2000;  2 257-61
• 5 Zhang H Q, Ding Y M, Chen G Y, Dong Y F, Zhu Y L. Studies on active constituents of root of Euphorbia ebracteolata Hayata.  Acta Botanica Sinica. 1987;  29 429-31
• 6 Dong Y F, Ding Y M. Acylploroglucinol derivatives from the root of Euphorbia ebracteolata Hayata.  Journal of Plant Resources and Environment. 1992;  1 1-3
• 7 Zhang H Q, Ding Y M. Studies on the active compounds B and C in the root of Euphorbia ebracteolata Hayata.  Journal of Plant Resources and Environment. 1992;  1 6-9
• 8 Lee S C, Ahn B T, Park W Y, Lee S H, Ro J S, Lee K S, Ryu E K. Pharmacognostic study on Euphorbia ebracteolata (I). Flavonoid constituents.  Saengyak Hakhoechi. 1992;  23 126-31
• 9 Ahn B T, Lee S C, Park W Y, Lee S H, Ro J S, Lee K S, Ryu E K. Pharmacognostic study on Euphorbia ebracteolata (II). On the chemical study of the tannins and related compounds.  Saengyak Hakhoechi. 1992;  23 211-7
• 10 Ahn B T, Oh K J, Ro J S, Lee K S. A new flavonoid from Euphorbia ebracteolata .  Planta Medica. 1996;  62 383-4
• 11 Ahn B T, Lee K S. Phenolic compounds from Euphorbia ebracteolata .  Saengyak Hakhoechi. 1996;  27 136-41
• 12 Mdee L K, Waibel R, Nkunya M H H, Jonker S A, Achenbach H. Rosane diterpenes and bis-dinorditerpenes from Hugonia casteneifolia .  Phytochemistry. 1998;  49 1107-13
• 13 Lal A R, Cambie R C, Rutledge P S, Woodgate P D. Ent-pimarane and Ent-abietane diterpenes from Euphorbia fidjiana .  Phytochemistry. 1990;  29 2239-46
• 14 Lal A R, Cambie R C, Rutledge P S, Woodgate P D. Ent-atisane diterpenes from Euphorbia fidjiana .  Phytochemistry. 1990;  29 1925-35
• 15 Ding Y L, Jia Z J. Tetracyclic diterpenols from Euphorbia sieboldiana .  Phytochemistry. 1991;  30 2413-5
• 16 Satti N K, Suri O P, Thaper R K, Kachroo P L. Ent-atisane-3β,16α,17-triol, a diterpene from Euphorbia acaulis .  Phytochemistry. 1988;  27 1530-1
• 17 Kigoshi H, Ichino T, Yamada K, Ijuin Y, Makita S F, Uemura D. Stereostructure and Bioactivities of Jolkinolide D.  Chemistry Letters. 2001;  30 518-9
• 18 Che C T, Zhou T X, Ma Q G, Qin G W, Williams I D, Wu H M, Shi Z S. Diterpenes and aromatic compounds from Euphorbia fischeriana .  Phytochemistry. 1999;  52 117-21