Antiproliferative Diterpenoids from the Leaves of Isodon rubescens

Abstract

A phytochemical study of Isodon rubescens leaves led to the isolation of five new diterpenoids, isorubesins A–E (1–5), and fifteen known diterpenoids. The structures of these new compounds were elucidated by spectroscopic evidence. Most of the diterpenoids were tested for cytotoxicity against NB4, A549, SHSY5Y, PC3, and MCF7 human tumor cells. Some of them showed potent inhibitory activity. Compound 5 is the first reported atisane-type diterpenoid from this plant.

Key words

Isodon rubescens - Labiatae - cytotoxicity - diterpenoid

References

• 1 Fujita E, Node M. Progress in the Chemistry of Organic Natural Products, Vol. 46. Vienna; Springer Verlag 1984: 77
• 2 Sun H D, Huang S X, Han Q B. Diterpenoids from Isodon species and their biological activities.  Nat Prod Rep. 2006;  23 673-678
• 3 Pharmacopoeia Commission .The Pharmacopoecia of the People's Republic of China. Beijing; People's Health Press 1977: 186
• 4 Han Q B, Xiang W, Li R T, Li M L, Li S W, Sun H D. Cytotoxic ent-kaurane diterpenoids from Isodon rubescens var. rubescens.  Planta Med. 2004;  70 269-272
• 5 Han Q B, Zhao A H, Zhang J X, Lu Y, Zhang L L, Zheng Q T, Sun H D. Cytotoxic constituents of Isodon rubescens var. lushiensis.  J Nat Prod. 2003;  66 1391-1394
• 6 Han Q B, Li M L, Li S H, Mou Y K, Lin Z W, Sun H D. Ent-kaurane diterpenoids from Isodon rubescens var. lushanensis.  Chem Pharm Bull. 2003;  51 790-793
• 7 Han Q B, Xiao W L, Shen Y H, Sun H D. Ent-kaurane diterpenoids from Isodon rubescens var. rubescens.  Chem Pharm Bull. 2004;  52 767-769
• 8 Huang S X, Xiao W L, Li L M, Li S H, Zhou Y, Ding L S, Lou L G, Sun H D. Bisrubescensins A–C: three new dimeric ent-kauranoids isolated from Isodon rubescens.  Org Lett. 2006;  8 1157-1160
• 9 Huang S X, Zhou Y, Pu J X, Li R T, Li X, Xiao W L, Lou L G, Han Q B, Ding L S, Peng S L, Sun H D. Cytotoxic ent-kauranoid derivatives from Isodon rubescens.  Tetrahedron. 2006;  62 4941-4947
• 10 Huang S X, Pu J X, Xiao W L, Li L M, Weng Z Y, Zhou Y, Han Q B, Peng S L, Ding L S, Lou L G, Sun H D. Ent-abietane diterpenoids from Isodon rubescens var. rubescens.  Phytochemistry. 2007;  68 616-622
• 11 Yang L B, Huang S X, Li L M, Zhao Y, Lei C, Xiao W L, Pu J X, Han Q B, Sun H D. Ent-kaurane diterpenoids from Isodon japonicus.  Helv Chim Acta. 2007;  90 2375-2379
• 12 Li L M, Li G Y, Huang S X, Li S H, Zhou Y, Xiao W L, Lou L G, Ding L S, Sun H D. 7, 20-Epoxy-ent-kauranoids from Isodon parvifolius.  J Nat Prod. 2006;  69 645-649
• 13 Fujita E, Nakamura S. Terpenoids. XXXIII. Chemical conversion of enmein into enmelol.  Chem Pharm Bull. 1975;  23 858-871
• 14 Li L M, Li G Y, Huang S X, Xiao W L, Liao X, Lou L G, Ding L S, Sun H D. Antiproliferative ent-kauranoids from Isodon parvifolius.  Planta Med. 2006;  72 740-745
• 15 Xiang W, Li R T, Wang Z Y, Li S H, Zhao Q S, Zhang H J, Sun H D. Ent-kaurene diterpenoids from Isodon oresbius.  Phytochemistry. 2004;  65 1173-1177
• 16 Na Z, Xiang W, Zhao Q S, Mei S X, Li C M, Lin Z W, Sun H D. A new ent-kauranoid from Isodon ternifolius.  Yunnan Zhiwu Yanjiu. 2002;  24 267-272
• 17 Zhao A H, Zhang Y, Xu Z H, Liu J W, Jia W. Immunosuppressive ent-kaurene diterpenoids from Isodon serra.  Helv Chim Acta. 2004;  87 3160-3166
• 18 Sun H D, Qiu S X, Lin L Z, Zhang R P, Zhou Y, Zheng Q T, Johnson M E, Fong Harry H S, Farnsworth N R, Cordell G A. Crystal structure of a 1: 1 complex of natural diterpenoids: absolute configurations and unambiguous NMR spectral assignments of neoangustifolin and epinodosinol.  J Nat Prod. 1997;  60 203-206
• 19 Huang S X, Zhou Y, Yang L B, Zhao Y, Li S H, Lou L G, Han Q B, Ding L S, Sun H D. Alboatisins A–C, ent-atisene diterpenoids from Isodon albopilosus.  J Nat Prod. 2007;  70 1053-1055
• 20 Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines.  J Natl Cancer Inst. 1991;  83 757-766