Cytotoxic Triterpenoids from the Fruits of Zizyphus jujuba

Abstract

The following eleven triterpenoic acids were isolated from the fruits of Zizyphus jujuba (Rhamnaceae): colubrinic acid, alphitolic acid, 3-O-cis-p-coumaroylalphitolic acid (3), 3-O-trans-p-coumaroylalphitolic acid (4), 3-O-cis-p-coumaroylmaslinic acid, 3-O-trans-p-coumaroylmaslinic acid, betulinic acid (7), oleanolic acid, betulonic acid (9), oleanonic acid and zizyberenalic acid. The in vitro cytotoxicities of the triterpenoic acids against K562, B16(F-10), SK-MEL-2, PC-3, LOX-IMVI, and A549 tumor cell lines were investigated by the sulforhodamin B (SRB) method. Among these compounds, the lupane-type triterpenes, such as compounds 3, 4, 7, and 9, showed high cytotoxic activities. In particular, the cytotoxic activities of 3-O-p-coumaroylalphitolic acids (compounds 3 and 4) were better than those of non-coumaroic triterpenenoids (compounds 7 and 9). These results suggest that the coumaroyl moiety at the C-3 position of the lupane-type triterpene may play an important role in enhancing cytotoxic activity.

References

• 1 Namba T. The Encyclopedia of Wakan-Yaku with Color Picture. Vol. I Osaka, Japan; Hoikusha Co 1993: 142- 4
• 2 Woo W S, Kang S S, Shim S H, Wagner H, Chari V M, Seligmann O, Obermeier G. The structure of spinosin (2″-O-β-glucosylswertisin) from Zizyphus vulgaris var. spinosus .  Phytochemistry. 1979;  18 353-5
• 3 Woo W S, Kang S S, Shim S H, Wagner H, Seligmann O, Chari V M. Acylated flavone-C-glycosides from the seeds of Zizyphus jujuba .  Phytochemistry. 1980;  19 2791-3
• 4 Naglaa M N. Phytoconstituents of Zizyphus spina-christi L. fruits and their antimicrobial activity.  Food Chemistry. 2002;  76 77-81
• 5 Yagi A, Okamura N, Haraguchi Y, Noda K, Nishioka I. Studies on the constituents of Zizyphi Fructus. II. Structure of new p-coumaroylates of maslinic acid.  Chem Pharm Bull. 1978;  26 3075-9
• 6 Tripathi M, Pandey M B, Jha R N, Pandey V B, Tripathi P N, Singh J P. Cyclopeptide alkaloids from Zizyphus jujuba .  Fitoterapia. 2001;  72 507-10
• 7 Lee S S, Lin B F, Karin C L. Three triterpene esters from Zizyphus jujuba .  Phytochemistry. 1996;  43 847-51
• 8 Lee S S, Shy S N, Karin C S. Triterpenes from Paliurus hemsleyanus .  Phytochemistry. 1997;  46 549-54
• 9 Yagi A, Okamura N, Haraguchi Y, Noda K, Nishioka I. Studies on the constituents of Zizyphi Fructus. I. Structure of three new p-coumaroylates of alphitolic acid.  Chem Pharm Bull. 1978;  26 1798-802
• 10 Kostas D, Costas D, Sofia M, Marios M, Theodoros T, Dimitrios K. Cytotoxic activity of kaempferol glycosides against human leukemic cell lines in vitro .  Pharmacological Research. 2000;  41 89-88
• 11 Darrick S, Kim H L, John M P, Emily P. Synthesis of betulinic acid derivatives with activity against human melanoma.  Bioorg Med Chem Lett. 1998;  8 1707-12
• 12 Skehan P, Streng R, Scudiero D, Monks A, McMahon J, Vistica D. New colorimetric cytotoxicity assay for anticancer-drug screening.  Journal of National Cancer Institute. 1990;  82 1007-13
• 13 Wu L, Smythe A M, Stinson S F, Mullendore L A, Monks A, Scudiero D A. Multidrug-resistant phenotype of disease-oriented panels of human tumor cell lines used for anticancer drug screening.  Cancer Research. 1992;  52 3029-34