Cytotoxic Cardenolide Glycosides from the Seeds of Antiaris toxicaria

Abstract

Bioassay-guided fractionation of the ethanolic extract from the seeds of Antiaris toxicaria led to the isolation of three new cardiac glycosides named toxicarioside J (1), toxicarioside K (2), and toxicarioside L (3), together with a known glucostrophalloside (4). The structures of the new compounds were elucidated by spectroscopic methods including HRESIMS, UV, IR, and 1D, 2D NMR techniques. The cytotoxic activities of these cardiac glycosides against human gastric (SGC-7901) and human hepatoma (SMMC-7721) cell lines were evaluated, and all of them exhibited significant cytotoxicity.

Antiaris toxicaria - Moraceae - cardenolides - SGC-7901 - SMMC-7721

References

• 1 Hauptman P J, Garg R, Kelly R A. Cardiac glycosides in the next millennium.  Prog Cardiovasc Dis. 1999;  41 247-254
• 2 Rose A M, Valdes jr. R. Understanding the sodium pump and its relevance to disease.  Clin Chem. 1994;  40 1674-1685
• 3 McConkey D J, Lin Y, Nutt L K, Ozel H Z, Newman R A. Cardiac glycosides stimulate Ca21 increases.  Cancer Res. 2000;  60 3807-3812
• 4 Zhang H F, Qian D Z, Tan Y S, Lee K A, Gao P, Ren Y R, Rey S, Hammers H, Chang D, Pili R, Dang C V, Liu J O, Semenza G L. Digoxin and other cardiac glycosides inhibit block tumor growth.  PNAS. 2008;  105 19579-19586
• 5 Mekhail T, Kaur H, Ganapat H R, Thomas B G, Elson P, Bukowski R M. Phase 1 trial of Anvirzel in patients with refractory solid tumors.  Invest New Drugs. 2006;  24 423-427
• 6 Bisset N G. The arrow and dart poisons of South-East Asia, with particular reference to the Strychnos species used in them. Part I. Indonesia, Borneo, Philippines, Hainan and Indo-China.  Lloydia. 1966;  29 1-18
• 7 Kopp B, Bauer W P, Bernkop-Schnuerch A. Analysis of some malaysian dart poisons.  J Ethnopharmacol. 1992;  36 57-62
• 8 Shrestha T, Kopp B N, Bisset G. The Moraceae-based dart poison of South America. Cardiac glycosides of Maquira and Naucleopsis species.  J Ethnopharmacol. 1992;  37 129-143
• 9 Mei W L, Gan Y J, Dai H F. Advances in studies on chemical constituents of Antiaris toxicaria and their pharmacological activities.  Chin Tradit Herb Drugs. 2007;  39 151-154
• 10 Dai H F, Gan Y J, Que D M, Wu J, Wen Z C, Mei W L. Two new cytotoxic cardenolides from the latex of Antiaris toxicaria.  J Asian Nat Prod Res. 2009;  11 832-837
• 11 Dai H F, Gan Y J, Que D M, Wu J, Wen Z C, Mei W L. A new cytotoxic 19-nor-cardenolide from the latex of Antiaris toxicaria.  Molecules. 2009;  14 3694-3699
• 12 Gan Y J, Mei W L, Zhao Y X, Dai H F. A new cytotoxic cardenolide from the latex of Antiaris toxicaria.  Chin Chem Lett. 2009;  20 450-452
• 13 Muhlradt P, Weiss E K, Reichstein T. Die Cardenolide der Samen von Antiaris toxicaria Lesch. 1. Mitteilung: Isolierung und Identifizierung von Glykosiden und Aglykonen, 258. Mitteilung.  Helv Chim Acta. 1964;  47 2164-2186
• 14 Jiang M M, Dai Y, Gao H, Zhang X, Wang G H, He J Y, Hu Q Y, Zeng J Z, Zhang X K, Yao X S. Cardenolides from Antiaris toxicaria as potent selective Nur77 modulators.  Chem Parm Bull. 2008;  56 1005-1008
• 15 Shi L S, Liao Y R, Su M J, Lee A S, Kuo P C, Damu A G, Kuo S C, Sun H D, Lee K H, Wu T S. Cardiac glycosides from Antiaris toxicaria with potent cardiotonic activity.  J Nat Prod. 2010;  73 1214-1222
• 16 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
• 17 Kopp B, Kubelka W. New cardenolides of Convallaria majalis.  Planta Med. 1982;  45 87-94
• 18 Chu H B, Tan N H. Iridoid glycosides from Pedicularis dolichocymba hand-mazz.  J Integr Plant Biol. 2006;  48 1250-1253
• 19 Lei Z H, Yanhara S, Nohara T, Tai B S, Xiong J Z, Ma Y L. Cardiac glycosides from Erysimum cheiranthoides.  Chem Pharm Bull. 2000;  48 290-292
• 20 Makarevich I F, Kolesnikov D G, Belokon V F. Cardiac glycosides of Cheiranthus allioni. IX.  Chem Nat Compd. 1974;  10 616-618