Soils on exposed Sunda shelf shaped biogeographic patterns in the equatorial forests of Southeast Asia.

The marked biogeographic difference between western (Malay Peninsula and Sumatra) and eastern (Borneo) Sundaland is surprising given the long time that these areas have formed a single landmass. A dispersal barrier in the form of a dry savanna corridor during glacial maxima has been proposed to explain this disparity. However, the short duration of these dry savanna conditions make it an unlikely sole cause for the biogeographic pattern.

Isolation and characterization of minor analogues of silvestrol and other constituents from a large-scale re-collection of Aglaia foveolata.

Two new minor silvestrol analogues [2'''-episilvestrol (1) and 2''',5'''-diepisilvestrol (2)], together with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds, were isolated from a large-scale re-collection of the CHCl(3)-soluble extract of the stem bark of Aglaia foveolata obtained in Kalimantan, Indonesia. The structures of the new compounds were established by interpretation of their spectroscopic data. All of the isolates were tested for cytotoxicity against HT-29 cells.

Proteasome-inhibitory and cytotoxic constituents of Garcinia lateriflora: absolute configuration of caged xanthones.

A new biflavonoid (1), a new xanthone enantiomer (2), five new caged xanthones (3-7), and several known compounds were isolated from the stem bark of Garcinia lateriflora, collected in Indonesia. The structures of the new compounds were determined by analysis of spectroscopic data, and the absolute configuration of the caged xanthones was shown for the first time at carbons 5, 7, 8, 8a, 10a, and 27, by analysis of COSY and NOESY NMR and ECD spectra. The biflavonoids exhibited proteasome inhibitory activity, and the known compound, morelloflavone (8) was found to have the greatest potency (IC(50) = 1.

Cytotoxic and NF-kappaB inhibitory constituents of Artocarpus rigida.

Four new prenylated flavonoids (1-4), a new stilbenoid (5), and nine known compounds were isolated from the twigs of Artocarpus rigida, collected in Indonesia. The structures of the new compounds were determined by analysis of their spectroscopic data, and the absolute configuration at C-12 of 1 and 2 and the known compounds artonin O (6), artobiloxanthone (7), and cycloartobiloxanthone (8) was determined from their CD and NMR spectroscopic data. Several of the compounds obtained were cytotoxic toward HT-29 human colon cancer cells, with the most potent being compound 2 and the known compounds 6 and 8.

Bioactivity-guided isolation of cytotoxic sesquiterpenes of Rolandra fruticosa.

Cytotoxicity-guided fractionation of a methanol extract of the leaves and twigs of Rolandra fruticosa using the HT-29 human colon cancer cell line led to the isolation of seven sesquiterpene lactones, including the hitherto unknown isorolandrolide, 13-methoxyisorolandrolide (1), and bourbonenolide, 2alpha,13-diacetoxy-4alpha-hydroxy-8alpha-isobutyroyloxybourbonen-12,6alpha-olide (2), as well as five known compounds, 13-acetoxyrolandrolide (3), 8-desacyl-13-acetoxyrolandrolide-8-O-tiglate (4), 2-epi-glaucolide E (5), 2alpha,13-diacetoxy-4alpha-hydroxy-8alpha-methacryloyloxybourbonen-12,6alpha-olide (6), and 2alpha,13-diacetoxy-4alpha-hydroxy-8alpha-tigloyloxybourbonen-12,6alpha-olide (7). The structures of the two sesquiterpenes were elucidated on the basis of spectroscopic methods. All isolates were evaluated for their cytotoxicity using the HT-29 cell line, and only 13-acetoxyrolandrolide (3) was found to possess a potent inhibitory effect against this cell line.

Isolation and Characterization of Aromatase Inhibitors from Brassaiopsis glomerulata (Araliaceae).

The hexane- and ethyl acetate-soluble extracts of the leaves of Brassaiopsis glomerulata (Blume) Regel (Araliaceae), collected in Indonesia, were found to inhibit aromatase, the rate-limiting enzyme in the production of estrogens from androgens, in both enzyme- and cell-based aromatase inhibition (AI) assays. Bioassay-guided fractionation led to the isolation of six known compounds of the steroid and triterpenoid classes (1-6) from the hexane extract, of which 6β-hydroxystimasta-4-en-3-one (5), was moderately active in the cell-based AI assay. Fractionation of the ethyl acetate extract afforded seven pure isolates (7-13) of the modified peptide, fatty acid, monoterpenoid, and benzenoid types, including six known compounds and the new natural product, N-benzoyl-L-phenylalanine methyl ester (9).

Bioactive constituents of the stem bark of Mitrephora glabra.

Bioactivity-guided fractionation of the stem bark of Mitrephora glabra yielded nine compounds, comprising three ent-kaurenoids (1-3), five polyacetylenic acids/esters (4-8), and one aporphine alkaloid, liriodenine (9). The structures of the six new compounds (1-3, 5, 7, and 8) were determined by spectroscopic data interpretation. All compounds were evaluated for their inhibitory activities against a panel of cancer cell lines and a battery of microorganisms.

Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen).

Bioassay-guided fractionation of a chloroform-soluble extract of Garcinia mangostana stem bark, using the HT-29 human colon cancer cell line and an enzyme-based ELISA NF-kappaB assay, led to the isolation of a new xanthone, 11-hydroxy-3-O-methyl-1-isomangostin (1). The structure of 1 was elucidated by spectroscopic data analysis. In addition, 10 other known compounds, 11-hydroxy-1-isomangostin (2), 11alpha-mangostanin (3), 3-isomangostin (4), alpha-mangostin (5), beta-mangostin (6), garcinone D (7), 9-hydroxycalabaxanthone (8), 8-deoxygartanin (9), gartanin (10), and cratoxyxanthone (11), were isolated.

Constituents of the Leaves and Stem Bark of Aglaia foveolata.

The previously known potent cytotoxic agent silvestrol (1) (0.002% w/w yield) and five new flavagline derivatives (2-6) were isolated from the leaves of Aglaia foveolata collected in Indonesia. The new compound 5 has an unprecedented cyclic amide moiety in its cyclopenta[b]benzopyran skeleton, while compound 6 is a novel benzo[b]oxepine derivative in which the oxepine ring is cleaved.

Dioxadispiroketal Compounds and a Potential Acyclic Precursor from Amomum aculeatum.

Four new compounds having an unusual 1,7-dioxadispiro[5.1.5.

Cytotoxic flavaglines and bisamides from Aglaia edulis.

Two new cyclopenta[b]benzofurans, aglaroxin A 1-O-acetate (2) and 3'-methoxyaglaroxin A 1-O-acetate (3), a new benzo[b]oxepine, 19,20-dehydroedulisone A (4), and five new cyclopenta[bc]benzopyrans, edulirin A (5), edulirin A 10-O-acetate (6), 19,20-dehydroedulirin A (7), isoedulirin A (8), and edulirin B (9), were isolated from the bark of Aglaia edulis, along with one known cyclopenta[b]benzofuran, aglaroxin A (1). Additionally, four new amides, aglamides A-D (10-13), as well as three known compounds, aglalactone, scopoletin, and 5-hydroxy-3,6,7,4'-tetramethoxyflavone, were isolated from the leaves and/or twigs of this species. The structures of the new compounds (2-13) were elucidated by interpretation of their spectroscopic data.

Cytotoxic clerodane diterpenoids from the leaves of Premna tomentosa.

Three clerodane diterpenoids, premnones A-C (1-3), were isolated from a chloroform-soluble fraction of Premna tomentosa along with four known flavonoids and three known triterpenoids. Among these isolates, premnones A-C exhibited cytotoxic activity when evaluated against a small panel of tumor cell lines. However, premnone A was found to be inactive when evaluated in a follow-up in vivo hollow fiber assay at the highest dose tested (50mg/kg), using LNCaP, Lu1, and MCF-7 cells.

Beccaridiol, an unusual 28-nortriterpenoid from the leaves of Diplectria beccariana.

A C29-triterpene, beccaridiol (1), a dihydrochalcone natural product, 2',4'-dihydroxy-3-(4-methoxyphenyl)-propiophenone (2), as well as three known compounds, 4'-hydroxy-1',2'-dihydro-beta-ionone, 4'-O-methyldavidigenin (3), and ursolic acid, have been isolated from an EtOAc-soluble extract of the leaves of Diplectria beccariana. Beccaridiol (1) was characterized as an ursane-type 28-nortriterpene possessing an unusual aromatic E-ring by spectroscopic data interpretation. The relative configuration of this unusual isolate was established by analyzing the observed NOESY NMR correlations, and the absolute stereochemistry of 1 was then determined based on the circular dichroism (CD) spectrum of its 2,3-di-p-bromobenzoate (1b) derivative.

Cytotoxic lignans from the stems of Helicteres hirsuta collected in Indonesia.

Cytotoxicity-guided fractionation of the stems of Helicteres hirsuta, of Indonesian origin, led to the isolation and identification of six lignans, namely, (+/-)-pinoresinol, (+/-)-medioresinol, (+/-)-syringaresinol, (-)-boehmenan, (-)-boehmenan H and (+/-)-trans-dihydrodiconiferyl alcohol. Of these isolates, (+/-)-pinoresinol exhibited potent cytotoxic effects when evaluated against a small panel of cancer cell lines.

A hexacyclic ent-trachylobane diterpenoid possessing an oxetane ring from Mitrephora glabra.

[chemical reaction: see text]. Three new ent-trachylobane diterpenoids (1-3) were isolated and structures elucidated from Mitrephora glabra Scheff. (Annonaceae).

Activity-guided isolation of cytotoxic constituents from the bark of Aglaia crassinervia collected in Indonesia.

Activity-guided fractionation of a CHCl(3)-soluble partition of the MeOH extract of the bark of Aglaia crassinervia collected in Indonesia led to the isolation of three new glabretal-type triterpenoids, aglaiaglabretols A-C (1-3), as well as nine known compounds, 3-epi-cabraleahydroxylactone (4), cabraleahydroxylactone (5), rocaglaol (6), 2beta,3beta-dihydroxy-5alpha-pregn-17(20)-(E)-16-one, scopoletin, and mixtures of cabraleadiol and epicotillol and of beta-sitosterol and stigmasterol. The structures of compounds 1-3 were determined on the basis of spectroscopic and chemical methods. The structure of aglaiaglabretol A (1) was confirmed by single-crystal X-ray analysis, and the absolute stereochemistry of this isolate was established by the Mosher ester method.

Activity-guided fractionation of the leaves of Ormosia sumatrana using a proteasome inhibition assay.

Activity-guided fractionation of a chloroform-soluble extract of the leaves of Ormosia sumatrana, using a proteasome inhibition assay, led to the isolation of a new A-type proanthocyanidin derivative, 3'-O-cinnamoylprocyanidin A-2 (1), and a new cerebroside, sumatranoside (2). The structures of these two isolates were determined as epicatechin-(2 beta-->O-->7',4 beta-->8')-epicatechin-3'-O-cinnamate (1) and 1-O-(beta-d-glucopyranosyl)-(2S,3S,4R)-2N-[(2'R)-2'-hydroxy-tetracosanoyl]-9Z-octadecene-1,3,4-triol (2), respectively, by spectroscopic and chemical methods. Sumatranoside (2) exhibited proteasome inhibitory activity with an IC(50) value of 30 microM.

Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2.

As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside.

Constituents of the seeds of Hernandia ovigera with inhibitory activity against cyclooxygenase-2.

A new dibenzylbutyrolactone lignan, (2 R,3 R)-5'-methoxyguayarol (1), was isolated from an EtOAc-soluble extract of the seeds of Hernandia ovigera using an in vitro activity-guided fractionation procedure based on the inhibition of cyclooxygenase-2. Also obtained were three known fatty acid derivatives, (S)-coriolic acid, (+/-)-12,13-epoxyoleic acid, and (+/-)-glycerol 1-monolinolate, and seven known lignans, epiashantin, dehydrodesoxypodophyllotoxin, dehydropodophyllotoxin, (-)-hernolactone, (-)-pinoresinol, (-)-syringaresinol, and (-)-yatein. The structure, including absolute stereochemistry, of compound 1 was determined using spectroscopic methods.

Cytotoxic and antimicrobial constituents of the bark of Diospyros maritima collected in two geographical locations in Indonesia.

Bioactivity-directed fractionation of extracts of two Diospyros maritima bark samples from Indonesia,one collected at sea level in a beach forest in Java and the other collected at a slight elevation away from the sea shore on the island of Lombok, yielded a diverse set of secondary metabolites. The naphthoquinone plumbagin (1), although found in extracts of both specimens, constituted a much larger percentage of the former sample, which also yielded a series of plumbagin dimers, maritinone (2), chitranone (3), and zeylanone (4). The latter sample yielded a new naphthoquinone derivative, (4S)-shinanolone (5), and a new natural product coumarin, 7,8-dimethoxy-6-hydroxycoumarin (6), along with three other analogues of plumbagin, 2-methoxy-7-methyljuglone (7), 3-methoxy-7-methyljuglone (8), and 7-methyljuglone (9).

Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.

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.

Saponins from the bark of Nephelium maingayi.

Activity-guided fractionation of the bark of Nephelium maingayi, collected in Indonesia, led to the isolation of six new saponins (1-6). The aglycon of 4 was determined to be a new compound, 7alpha-methoxyerythrodiol, and those of 1-3 and of 5 and 6 were identified as erythrodiol and maniladiol (16beta-hydroxyamyrin), respectively. The structures of 1-6 were determined on the basis of spectral data interpretation, and the absolute configurations of their component monosaccharides were determined as their thiazolidine derivatives after acid hydrolysis.

Constituents of the stem bark of Pongamia pinnata with the potential to induce quinone reductase.

Activity-guided fractionation of the petroleum ether and ethyl acetate extracts of the stem bark of Pongamia pinnata, using cultured Hepa 1c1c7 mouse hepatoma cells to evaluate quinone reductase (QR) inducing activity, led to the isolation of four new flavanone derivatives (1-4), one new flavone (5), one new chalcone (6), and 13 known compounds of the flavonoid, terpenoid, and fatty acid types. The structures of 1-6 were characterized on the basis of the interpretation of their spectroscopic data. The absolute stereochemistry of compounds 1-4 was determined from their CD data and by Mosher ester determination.

Cytotoxic flavone analogues of vitexicarpin, a constituent of the leaves of Vitex negundo.

Bioassay-guided fractionation of the chloroform-soluble extract of the leaves of Vitex negundo led to the isolation of the known flavone vitexicarpin (1), which exhibited broad cytotoxicity in a human cancer cell line panel. In an attempt to increase the cytotoxic potency of 1, a series of acylation reactions was performed on this compound to obtain its methylated (2), acetylated (3), and six new acylated (4-9) derivatives. Compound 9, the previously unreported 5,3'-dihexanoyloxy-3,6,7,4'-tetramethoxyflavone, showed comparative cytotoxic potency to compound 1 and was selected for further evaluation.