Two new compounds, an ent-isopimarane-type diterpene, 3alpha,12alpha-dihydroxy-ent-8(14),15-isopimaradien-18-al (1), and a dihydrobenzo[b]furan neolignan, (-)-trans-9-acetyl-4,9'-di-O-methyl-3'-de-O-methyldehydrodiconiferyl alcohol (2), along with five known compounds, 7,7'-dihydroxy-6,8'-bicoumarin (bicoumol) (3), 3,4-dimethoxycinnamaldehyde (4), 6-hydroxy-7-methoxycoumarin (isoscopoletin), N-butylaniline, and vanillin, have been isolated from an ethyl acetate-soluble extract of the stem wood of Euphorbiaquinquecostata. The structures of compounds 1 and 2 were elucidated on the basis of spectroscopic data interpretation, and single-crystal X-ray diffraction analysis was used to confirm the structure and relative stereochemistry of 1. The absolute configuration of 1 was established by a convenient Mosher ester procedure in which the sample was treated with MTPA chlorides in deuterated pyridine directly in NMR tubes. All isolates were evaluated for the induction of quinone reductase in Hepa1c1c7 hepatoma cells and for the inhibition of the transformation of murine epidermal JB6 cells.

Two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol (1) and episilvestrol (2), were isolated from the fruits and twigs of Aglaia silvestris by bioassay-guided fractionation monitored with a human oral epidermoid carcinoma (KB) cell line. Additionally, two new baccharane-type triterpenoids, 17,24-epoxy-25-hydroxybaccharan-3-one (3) and 17,24-epoxy-25-hydroxy-3-oxobaccharan-21-oic acid (4), as well as eleven known compounds, 1beta,6alpha-dihydroxy-4(15)-eudesmene (5), ferulic acid (6), grasshopper ketone (7), apigenin, cabraleone, chrysoeriol, 1beta,4beta-dihydroxy-6alpha,15alpha-epoxyeudesmane, 4-hydroxy-3-methoxyacetophenone, 4-hydroxyphenethyl alcohol, ocotillone, and beta-sitosterol 3-O-beta-D-glucopyranoside, were also isolated and characterized. The structures of compounds 1-4 were elucidated by spectroscopic studies and by chemical transformation. The absolute stereochemistry of silvestrol (1) was established by a X-ray diffraction study of its di-p-bromobenzoate derivative, and the structure of 3 was also confirmed by single-crystal X-ray diffraction. The isolates and chemical transformation products were evaluated for cytotoxicity against several human cancer cell lines, and silvestrol (1) and episilvestrol (2) exhibited potent in vitro cytotoxic activity. Silvestrol (1) was further evaluated in vivo in the hollow fiber test and in the murine P-388 leukemia model.

Purification of a n-BuOH-soluble partition of the MeOH extract of Morinda citrifolia (Noni) fruits led to the isolation of two new iridoid glucosides, 6alpha-hydroxyadoxoside (1) and 6beta,7beta-epoxy-8-epi-splendoside (2), as well as 17 known compounds, americanin A (3), narcissoside (4), asperuloside, asperulosidic acid, borreriagenin, citrifolinin B epimer a, citrifolinin B epimer b, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, d-glucose, d-mannitol, methyl alpha-d-fructofuranoside, methyl beta-d-fructofuranoside, nicotifloroside, and beta-sitosterol 3-O-beta-d-glucopyranoside. The structures of the new compounds were determined by spectroscopic data interpretation. Compound 4, borreriagenin, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, methyl alpha-d-fructofuranoside, and methyl beta-d-fructofuranoside were isolated for the first time from M. citrifolia. The antioxidant activity was evaluated for all isolates in terms of both DPPH and ONOO(-) bioassays. The neolignan, americanin A (3), was found to be a potent antioxidant in these assays.

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Previous collaborative work by our group has led to the discovery of several plant isolates and derivatives with activities in in vivo models of cancer chemoprevention, including deguelin, resveratrol, bruceantin, brassinin, 4¢-bromoflavone, and oxomate. Using a panel of in vitro bioassays to monitor chromatographic fractionation, a diverse group of plant secondary metabolites has been identified as potential cancer chemopreventive agents from mainly edible plants. Nearly 50 new compounds have been isolated as bioactive principles in one or more in vitro bioassays in work performed over the last five years. Included among these new active compounds are alkaloids, flavonoids, stilbenoids, and withanolides, as well as a novel stilbenolignan and the first representatives of the norwithanolides, which have a 27-carbon atom skeleton. In addition, over 100 active compounds of previously known structure have been obtained. Based on this large pool of potential cancer chemopreventive compounds, structureactivity relationships are discussed in terms of the quinone reductase induction ability of flavonoids and withanolides and the cyclooxygenase-1 and -2 inhibitory activities of flavanones, flavones and stilbenoids. Several of the bioactive compounds were found to be active when evaluated in a mouse mammary organ culture assay, when used as a secondary discriminator in our work. The-2,4,2¢,4¢-tetrahydroxychalcone 11¢-O-coumarate, isolicoflavonol, isoliquiritigenin, and ixocarpalactone A are regarded as promising leads as potential cancer chemopreventive agents.

Morinda citrifolia, commonly known as noni, has a long history of utilization throughout much of tropical Polynesia and is considered to be the second most important medicinal plant in the Hawaiian Islands. Recently, the use of noni as a dietary supplement in the United States has greatly increased. Bioassay-guided fractionation of a dichloromethane-soluble partition of a MeOH extract of noni fruits has led to the isolation of an extremely potent quinone reductase inducer, 2-methoxy-1,3,6-trihydroxyanthraquinone (1). This new anthraquinone (1) was nearly 40 times more potent than a positive control, l-sulforaphane. Furthermore, compound 1 demonstrated no discernible cytotoxicity at the highest dose tested. In addition to compound 1, 11 known compounds were also isolated and identified in the present investigation. This is the first report of the isolation of anthraquinones from noni fruits.

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