Planta Med 2007; 73(14): 1486-1490
DOI: 10.1055/s-2007-990258
Natural Product Chemistry
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Agents from Terminalia arjuna

Mohit Saxena1 , Uzma Faridi2 , Rupal Mishra1 , M. M. Gupta1 , M. P. Darokar2 , S. K. Srivastava1 , Digvijai Singh1 , Suaib Luqman2 , S. P. S. Khanuja2
  • 1Analytical Chemistry Division, Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, India
  • 2Genetic Resource and Biotechnology Division, Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow, India
Further Information

Publication History

Received: June 4, 2007 Revised: September 26, 2007

Accepted: October 2, 2007

Publication Date:
16 November 2007 (online)

Abstract

Although a number of chemicals have been isolated from Terminalia arjuna, only a few have been evaluated for their biological significance. As a part of our drug discovery programme for cytotoxic agents from Indian medicinal plants, four novel cytotoxic agents arjunic acid (1), arjungenin (2), arjunetin (3) and arjunoglucoside I (4) were isolated from the bark of T. arjuna. Out of the four compounds, arjunic acid (1) was significantly active against the human oral (KB), ovarian (PA 1) and liver (HepG-2 & WRL-68) cancer cell lines. Further, the most active compound arjunic acid was converted into seven semi-synthetic ester derivatives 5 - 11. 2-O-Palmitoyl arjunic acid (6) showed two times more activity, while 2, 3-di-O-acetyl-, 2-O-p-anisoyl-, 2, 3-di-O-benzoyl- and 2, 3-di-O-p-nitrobenzoyl arjunic acid (7 - 10) showed 1.7 - 2.3 times less activity than the cytotoxic drug vinblastine against the liver cancer cell lines HepG-2 and WRL-68 respectively.

References

  • 1 Srivastava S K, Joshi B S, Newton M G, Lee D, Pelletier S W. Heterolytic fragmentation of deltaline, A norditerpenoid alkaloid.  Tetrahedron Lett. 1995;  36 519-22.
  • 2 Sparg S G, Light M E, Vanstadan J. Biological activities and distribution of plant saponins.  J Ethnopharmacol. 2004;  94 219-43.
  • 3 Liu J. Oleanolic acid and ursolic acid: Research perspectives.  J Ethnopharmacol. 2005;  100 92-4.
  • 4 Fukuda Y, Sakai K, Matsunaga S, Tokuda H, Tanaka R. Cancer chemopreventive effect of orally administrated lupane-type triterpenoid on ultraviolet light B induced photo carcinogenesis of hairless mouse.  Cancer Lett. 2006;  240 94-101.
  • 5 Novonty L, Vachalkaova A, Biggs D. Ursolic acid: an anti-tumorigenic and chemopreventive activity.  Neoplasma. 2001;  48 241-3.
  • 6 Haridas V, Arntzen C, Gutterman J U. Avicins, a family of triterpenoid saponins from Acacia victoriae (Betham), inhibit activation of nuclear factor-kB by inhibiting both its nuclear localization and ability to bind DNA.  J Proc Natl Acad Sci USA. 2001;  98 11 557-62.
  • 7 Jung H, Nam J, Croi J, Lee K, Park H. 19α-Hydroxyursane-type triterpenoids: antinociceptive anti-inflammatory principles of the roots of Rosa rugosa .  Biol Pharm Bull. 2005;  28 101-4.
  • 8 Battinelli L, Mangoni F, Lichtner M, Mazzanti G, Saija A, Mastroianni C. et al . Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells.  Planta Med. 2003;  69 910-3.
  • 9 Keda T, Yokomizo K, Okawa M, Tsuchihashi R, Kinjo J, Nohara T. et al . Anti Herpes virus type 1 activity of oleanane-type triterpenoids.  Biol Pharm Bull. 2005;  28 1779-81.
  • 10 Cheng H Y, Lin C C, Lin T C. Anti Herpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn.  Antiviral Res. 2002;  55 447-55.
  • 11 Kurup P NV, Ramdas V NK, Joshi P. Handbook of medicinal plants. New Delhi 1979: 39.
  • 12 Gauthaman K, Banerjee S K, Dinda A K, Ghosh C C, Maulik S K. Terminalia arjuna (Roxb.) Protects rabbit heart against ischemic-reperfusion injury: role of antioxidant enzymes and heat shock protein.  J Ethnopharmacol. 2005;  96 403-9.
  • 13 Dwivedi S, Aggarwal A, Agarwal M P, Rajpal S. Role of Terminalia arjuna in ischaemic mitral regurgitation.  Int J Cardiol. 2005;  100 507-8.
  • 14 Pawar R S, Bhutani K K. Effect of oleanane triterpenoid from Terminalia arjuna - a cardioprotective drug on the process of respiratory ox burst.  Phytomedicine. 2005;  12 391-3.
  • 15 Anjaneyulu A SR, Rama Prasad A V. Structure of terminic acid, a dihydroxytriterpene carboxylic acid from Terminalia arjuna .  Phytochemistry. 1983;  22 993-8.
  • 16 Tripathi V K, Pandey V B, Udupa K N, Rücker G. Arjunolitin, a triterpene glycoside from Terminalia arjuna .  Phytochemistry. 1992;  31 349-51.
  • 17 Yadav R N, Rathore K. A new cardenolide from the roots of Terminalia arjuna .  Fitoterapia. 2001;  72 459-61.
  • 18 Dwivedi S, Udupa N. Terminalia arjuna: pharmacognosy, phytochemistry, pharmacology, and clinical use. A review.  Fitoterapia. 1989;  60 413-20.
  • 19 Pettit G R, Hoard M S, Doubek D L, Schmidt J M, Pettit R K, Tackett L P. et al . Antineoplastic agents 338. The cancer cell growth inhibitory constituents of Terminalia arjuna (Combretaceae).  J Ethnopharmacol. 1996;  53 57-63.
  • 20 Kaur B SJ, Grover I S, Kumar S. Antimutageninc potential of ellagic acid isolated from Terminalia arjuna .  Ind J Exp Biol. 1997;  35 478-81.
  • 21 Kandil F E, Mahmood I N. A tannin anti-cancer promotor from Terminalia arjuna .  Phytochemistry. 1998;  47 1567-8.
  • 22 Srivastava S K, Khan M, Khanuja S PS. Process for isolation of anticancer agent camptothecin from Nothapodytes foetida . US Patent 68,936,698: 2005.
  • 23 Khanuja S PS, Tiruppadiripuliyur R SK, Gupta V K, Chand P, Garg A, Srivastava S K. et al .Antimicrobial and anticancer properties of methyl-beta-orcinolcarboxylate from lichen (Everniastrum cirrhatum). US Patent 20,040,198,815: 2004.
  • 24 Saxena M, Faridi U, Srivastava S K, Darokar M P, Mishra R, Pal A nirban. et al . A cytotoxic and hepatoprotective agent from Withania somnifera and biological evaluation of its ester derivatives.  Nat Prod Commun. 2007;  2 775-8.
  • 25 Anjaneyulu A SR, Rama Prasad A V. Chemical examination of the roots of Terminalia arjuna-The structures of arjunoside III and arjunoside IV, two new triterpenoid glycosides.  Phytochemistry. 1982;  21 2057-60.
  • 26 Row L R, Murthy P S, Subba Rao G SR, Sastry C SP, Rao K VJ. Chemical examination of Terminalia species: Part XII Isolation and structure determination of arjunic acid, a new trihydroxy triterpene carboxylic acid from Terminalia arjuna .  Ind J Chem. 1970;  8 716-21.
  • 27 Honda T, Murae T, Tsuyuki T, Takahasi T, Sawai M. Arjungenin, arjunglucoside I and arjunglucoside II. A new triterpene glucoside from Terminalia arjuna .  Bull Chem Soc (Japan). 1976;  49 3213-8.
  • 28 Tsuyuki T, Hamada Y, Honda T, Takahashi T, Matsushita K. A new triterpene glucoside from Terminalia arjuna Arjunglucoside II.  Bull Chem Soc (Japan). 1979;  52 3127-8.
  • 29 Woerdenbag H J, Moska T A, Pras N, Malingre T M. Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumour cells.  J Nat Prod. 1993;  56 849-56.
  • 30 Liu J. Oleanolic acid and ursolic acid: Research perspectives.  J Ethnopharmacol. 2005;  100 92-4.
  • 31 Fukuda Y, Sakai K, Matsunaga S, Tokuda H, Tanaka R. Cancer chemopreventive effect of orally administrated lupane-type triterpenoid on ultraviolet light B induced photocarcinogenesis of hairless mouse.  Cancer Lett. 2006;  240 94-101.
  • 32 Konopleva M, Tsao T, Estrov Z, Lee R M, Wang R Y, Jackson C E. et al . The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces caspase-dependent and -independent apoptosis in acute myelogenous leukemia.  Cancer Res. 2004;  64 7927-35.
  • 33 Pawar R S, Balachandran P, Pasco D S, Khan I A. Cytotoxicity studies of triterpenoids from Akebla trifoliate and Clematis lingustifolia .  Acta Hort. 2006;  720 171-8.
  • 34 Wang Z -P. Saponins as anticancer agent. US Patent 20,050,175,623A1: 2005

S. K. Srivastava

Central Institute of Medicinal and Aromatic Plants

P.O. CIMAP

Lucknow - 226015

India

Phone: +91-522-235-8723

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