Cytotoxic Cucurbitane-Type Triterpenoids fromElaeocarpus 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 microM.

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

“…Cucurbitacin D, isolated from Trichosanthes kirilowii, was shown to suppress the growth of Hep3b cells by apoptosis through caspase-3 and phosphorylation of JNK protein [85] . Meng et al [86] isolated cucurbitacins D and I from Elaeocarpus hainanensis and reported strong cytoxic effects of these compounds against Bel-7402 cells. Echinocystic acid, a triterpene present in various herbs, is used for medicinal purposes in many Asian countries.…”

“…Meng et al [86] Echinocystic acid Exhibited antiproliferative effect against HepG2 cells ↑apoptosis; ↓Bcl-2; ↑caspase-3, -9, -8; ↑PARP cleavage; ↓∆Ψm; ↓cyt. c; ↑p38; ↑JNK 15-100 μmol/L Tong et al [87] Escin Demonstrated inhibitory effects on cell viability of HepG2 cells ↑apoptosis; ⊥G1/S; ↑AIF; ↑cyt.…”

Isolation, structure elucidation, and biological evaluation of 16,23-epoxycucurbitacin constituents from Eleaocarpus chinensis

“…28 and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (13). 11 Moreover, from the less potently cytotoxic CHCl 3 extract of the stem bark of the same plant, two additional new cucurbitacins, elaeocarpucins G (7) and H (8), were purified. Herein, we report the isolation and structure elucidation of the eight new compounds, 1-8, as well as the biological assessment of all isolates obtained in this investigation.…”

“…2 Elaeocarpus is a large genus comprised of 350-360 species distributed from Madagascar to Oceania, with the highest concentration occurring in Borneo and Papua New Guinea. 3,4 Previous phytochemical work has resulted in the isolation of anthocyanins, 5 cucurbitacin-type triterpenoids, [6][7][8][9][10][11][12] flavonoids, 13,14 other phenolic derivatives 13 , and indolizidine alkaloids, [15][16][17] Among these compounds, cucurbitacins and their derivatives are tetracyclic triterpenoids obtained initially from plants of the family Cucurbitaceae, and are reported to have anticancer, antifertility, anti-inflammatory, cytotoxic, and purgative activities. 18,19 Although the development of cucurbitacins as anticancer drug candidates has been hindered by their non-specific cytotoxicity, there is much interest in the relationship of structure to cytotoxicity within this compound class.…”

“…Scrutiny of the NAPRALERT SM (Natural Products Alert) database 24 indicated that more than 150 compounds have been isolated from the genus Elaeocarpus, with most of the cytotoxic compounds known being cucurbitacin-type triterpenes. In order to decide whether or not to further pursue this lead, the CHCl 3 -soluble extract of E. chinensis fruits was subjected to an LC-MS dereplication procedure, which revealed the probable presence of the known cytotoxic cucurbitacins, cucurbitacin D (9), 3-epi-isocucurbitacin D (10) and 25-Oacetylcucurbitacin F (11). In addition, certain unknown cytotoxic compounds corresponding to possible molecular formulas of C 30 H 44 O 5 and C 30 H 46 O 5 were evident.…”