Two Novel ent-Kauranoid Diterpenoids from Isodon japonica Leaves

Abstract

Two novel ent-kaurane diterpenoids, taihangjaponicain A (1), and taihangjaponicain B (2), and nine known diterpenoids, epinodosin (3), oridonin (4), epinodosinol (5), lasiokaurin (6), 1α-O-β-D-glucopyranosylenmenol (7), lasiodonin (8), rabdosichuanin D (9), shikokianin (10) and rabdoternin A (11) were isolated from I. japonica leaves. The structures of the two new compounds were elucidated using 1-D and 2-D NMR spectroscopy. Compounds 1 and 3 - 11 were tested against HL-60, HO-8910 and A-549 human tumor cells. Compounds 4, 6 and 10 showed significant cytotoxicity against HL-60 cells with IC₅₀ values of 4.6, 2.0 and 3.4 μM, respectively, and against A-549 cells with IC₅₀ values of 17.5, 11.4 and 18.8 μM, respectively. Compound 6 exhibited moderate cytotoxicity against HO-8910 cells with an IC₅₀ value of 17.9 μM.

Key words

Isodon japonica - Labiatae - diterpene dimer - ent-kauranoids - cytotoxicity

References

• 1 Sun H D, Xu Y L, Jiang B. Diterpenoids from Isodon species. Beijing; Science Press 2001: pp 2-3
• 2 Zhao Q Z, Chao J H, Wang H Q, Sun H D. Studies on the chemical constituents of Isodon japonica .  Chin Tradit Herbal Drugs. 1984;  15 49-52
• 3 Han Q B, Zhang J X, Shen Y H, Sun H D. Diterpenoids from Isodon japonica .  Chin J Nat Med. 2003;  1 16-20
• 4 Li B L. Taibaijaponicains C and D: two new diterpenoids from Isodon japonica .  Planta Med. 2002;  68 477-9
• 5 Wang M T, Zhao T Z, Li J C, Liu C J, An X Z. The structures of rabdosinate and rabdosinatol.  Acta Chim Sin. 1987;  45 871-4
• 6 Li J C, Liu C J, An X Z, Wang M T, Zhao T Z, Yu S Z. Studies on the antitumor constituents of Rabdosia japonica (Burman f.) Hara.  Acta Pharm Sin. 1982;  17 682-7
• 7 Xu F M, Hu H P, Wang Z Q. Studies on the diterpenoid constituents of Isodon japonica .  Chin J Chin Med. 1996;  21 678-9
• 8 Zang J X, Han Q B, Zhao Q S, Li S H, Su H D. Two new ent-kaurane diterpenoids from Isodon japonica .  Chin Chem Lett. 2002;  13 1075-8
• 9 Zang J X, Han Q B, Zhao A H, Sun H D. Diterpenoids from Isodon japonica .  Fitoterapia. 2003;  74 435-8
• 10 Li B L, Tian X H. Enmein type diterpenoids from Isodon japonica .  Phytochemistry. 2001;  58 543-6
• 11 Ma J, Jin X, Yang L, Liu Z L. Diarylheptanoids from the rhizomes of Zingiber officinale .  Phytochemistry. 2004;  65 1137-43
• 12 Sun H D, Xu Y L, Jiang B. Diterpenoids from Isodon species. Beijing; Science Press 2001: p 291
• 13 Liu H M, Yan X B, Kiuchi F, Liu Z Z. A New diterpene glycoside from Rabdosia rubescens .  Chem Pharm Bull. 2000;  48 148-9
• 14 Gao Y H, Wan Z X, Xu C R, Zhu Y. Studies on the chemical constituents of Rabdosia nervosa .  J Chin Med Mat. 1994;  17 28-9
• 15 Takeda Y, Fujita T, Chen C C. Structures of lasiocarpanin, rabdolasional, and carpalasionin: new diterpenoids from Rabdosia lasiocarpa . Chem Lett 1982: 833-6
• 16 Huang H, Zhang H J, Sun H D. Diterpenoids from Rabdosia setschwanensis .  Phytochemistry. 1990;  29 2591-5
• 17 Takeda Y, Takeda K, Fujita T, Sun H D. Studies on the diterpenoid constituents of Rabdosia ternifolia .  Chem Pharm Bull. 1990;  38 439-42
• 18 Price P, Mcmillan T J. Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation.  Cancer Res. 1990;  50 1392-7
• 19 Han Q B, Liu Y, Zhang L L, Zheng Q T, Sun H D. Novel ent-kaurane dimers from Isodon rubescens var. rubescens .  Tetrahedron Lett. 2004;  45 2833-7