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.
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.
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.
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.
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.
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.
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.
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.
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.