Cytotoxic Cucurbitane-Type Triterpenoids from Elaeocarpus hainanensis

Abstract

Bioassay-guided fractionation of the crude extract of Elaeocarpus hainanensis (Elaeocarpaceae), using the proliferation of non-small cell lung cancer A549/ATCC and human hepatocellular carcinoma BEL-7402 cells as a monitor, led to the isolation of ten cucurbitane-type triterpenoids, including three new compounds (1 – 3) and seven known compounds (4 – 10). Their structures were determined on the basis of spectroscopic analyses, chemical methods, and comparison with spectroscopic data in literature. The two known compounds, cucurbitacins D (5) and I (10) were found to exhibit the strongest cytotoxicity against A549/ATCC and BEL-7402 cells in vitro with IC₅₀ values of less than 1 μM.

Key words

Elaeocarpus hainanensis - Elaeocarpaceae - cucurbitane - triterpenoids - cytotoxicity

References

• 1 Newman D J, Cragg G M, Snader K M. Natural products sources of new drugs over the period 1981 – 2002.  J Nat Prod. 2003;  66 1022-37
• 2 Hong Kong H erbarium, South China Botanical Garden C AS. Check list of Hong Kong plants. Hong Kong; Agriculture, Fisheries and Conservation Department 2001: 75
• 3 Ito A, Chai H B, Lee D, Kardono L BS, Riswan K, Farnsworth N R. et al . Ellagic acid derivatives and cytotoxic cucurbitacins from Elaeocarpus mastersii.  Phytochemistry. 2002;  61 171-4
• 4 Fang X D, Phoebe J RCH, Pezzuto J M, Fong H S, Farnsworth N R, Yellin B. et al . Plant anticancer agents, XXXIV. cucurbitacins from Elaeocarpus dolichostylus.  J Nat Prod. 1984;  47 988-93
• 5 Carroll A R, Arumugan G, Quinn R J, Redburn J, Guymer G, Grimshaw P. Grandisine A and B, novel indolizidine alkaloids with human δ-opioid receptor binding affinity from the leaves of the Australian rainforest tree Elaeocarpus grandis.  J Org Chem. 2005;  70 1889-92
• 6 Katavic P L, Venables D A, Forster P I, Guymer G, Carroll A R. Grandisines C – G, indolizidine alkaloids from the Australian rainforest tree Elaeocarpus grandis.  J Nat Prod. 2006;  69 1295-9
• 7 Katavic P L, Venables D A, Rali T, Carroll A R. Habbemines A and B, pyrrolidine alkaloids with human δ-opioid receptor binding affinity from the leaves of Elaeocarpus habbemensis.  J Nat Prod. 2007;  70 866-8
• 8 Katavic P L, Venables D A, Rali T, Carroll A R. Indolizidine alkaloids with δ-opioid receptor binding affinity from the leaves of Elaeocarpus fuscoides.  J Nat Prod. 2007;  70 72-5
• 9 Elkhateeb A, Takahashi S K, Matsuura H, Yamasaki M, Yamato O, Maede Y. et al . Anti-babesial ellagic acid rhamnosides from the bark of Elaeocarpus parvifolius.  Phytochemistry. 2005;  66 2577-80
• 10 Muňoz O, Delporte C, Backhouse N, Erazo S, Negrete R, Maldonado S. et al . A new cucurbitacin glycosides from Kageneckia oblonga (Rosaceae).  Z Naturforsch. 2000;  55 141-5
• 11 Seger C, Sturm S, Haslinger E, Stuppner H. NMR signal assignment of 22-deoxocucurbitacin D and cucurbitacin D from Ecballium elaterium L. (Cucurbitaceae).  Monatsheft Chem. 2005;  136 1645-9
• 12 Sarker S D, Whiting P, ik V, Dinan L. Ecdysteroid antagonists (cucurbitacins) from Physocarpus opulifolius (Rosaceae).  Phytochemistry. 1999;  50 1123-8
• 13 Afifi M S, Ross S A, Elsohly M A, Naeem Z E, Halaweish F T. Cucurbitacins of Cucumis prophetarum.  J Chem Ecol. 1999;  25 847-60
• 14 Fujita S, Kasai R, Ohtani K, Yamasaki K, Chiu M H, Nie R L. et al . Dammarane glycosides from aerial parts of Neoalsomitra integrifoliola.  Phytochemistry. 1995;  38 465-72
• 15 Farias M R, Schenkel E P, Mayer R, Rücher G. Cucurbitacins as constituents of Wilbrandia ebracteata.  Planta Med. 1993;  59 272-5
• 16 Velde V V, Lavie D. ¹³C-NMR spectroscopy of cucurbitacins.  Tetrahedron. 1983;  39 317-21
• 17 Chen C T, Fang X D, Phoebe J RCH, Kinghorn A D, Farnsworth N R, Yellin B. et al . High-field 1H-NMR spectral analysis of some cucurbitacins.  J Nat Prod. 1985;  48 429-34
• 18 Schenkel E P, Farias M R, Mayer R, Breitmaier E, Rücher G. Cucurbitacins from Wilbrandia ebracteata.  Phytochemistry. 1992;  31 1329-33
• 19 Chen J C, Chiu M H, Nie R L, Cordell G A, Qiu S X. Cucurbitacins and cucurbitane glycosides: structures and biological activities.  Nat Prod Rep. 2005;  22 386-99
• 20 Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D. et al . Feasibility of a high-flux anticancer drug screen utilizing a diverse panel of human tumor cell lines in culture.  J Natl Cancer Inst. 1991;  83 757-66