Neolignans and other metabolites from Ocotea cymosa from the Madagascar rain forest and their biological activities.

Ten new neolignans including the 6'-oxo-8.1'-lignans cymosalignans A (1a), B (2), and C (3), an 8.O.6'-neolignan (4a), ococymosin (5a), didymochlaenone C (6a), and the bicyclo[3.2.1]octanoids 7-10 were isolated along with the known compounds 3,4,5,3',5'-pentamethoxy-1'-allyl-8.O.4'-neolignan, 3,4,5,3'-tetramethoxy-1'-allyl-8.O.4'-neolignan, didymochlaenone B, virologin B, ocobullenone, and the unusual 2'-oxo-8.1'-lignan sibyllenone from the stems or bark of the Madagascan plant Ocotea cymosa. The new 8.O.6'-neolignan 4a, dihydrobenzofuranoid 5a, and the bicyclo[3.2.1]octanoid 7a had in vitro activity against Aedes aegypti, while the new compounds 5a, 7a, 8, and 10a and the known virolongin B (4b) and ocobullenone (10b) had antiplasmodial activity. We report herein the structure elucidation of the new compounds on the basis of spectroscopic evidence, including 1D and 2D NMR spectra, electronic circular dichroism, and mass spectrometry, and the biological activities of the new and known compounds.

An antiproliferative xanthone of Symphonia pauciflora from the Madagascar rainforest.

Investigation of a Malagasy endemic plant identified as Symphonia pauciflora Baker (Clusiaceae) for antiproliferative activities against the A2780 ovarian cancer cell line led to the isolation of a new compound identified as 2-(3,3-dimethylallyl)-7-methoxy-l,5,6-trihydroxy-2",2"-dimethylpyrano(6",5":3,4) xanthone (1) and the two known guttiferones A (2) and I (3). The structure elucidation of 1 was based on the analysis of its 1D and 2D NMR and mass spectral data. Compound 1 showed good antiproliferative activity with an IC50 value of 3.8 microM against the A2780 human ovarian cancer cell line, while the known guttiferone analogues (2 and 3) exhibited moderate activities with IC50 values of 8.3 microM and 7.8 microM, respectively.

A new labdane diterpene from Vitex cauliflora Moldenke from the Madagascar rainforest.

Fractionation of an antiplasmodial ethanolic extract from the aerial parts of Vitex cauliflora led to the isolation of the new labdane diterpene 1 together with the known triterpene uvaol. The structure of the new compound 1 was established as 3-oxo,15,17,18-triacetoxy-labda-7,13E-diene on the basis of spectroscopic data (1D and 2D NMR, MS).

Antiproliferative compounds of Artabotrys madagascariensis from the Madagascar rainforest.

Bioassay-guided fractionation of an ethanol extract of Artabotrys madagascariensis led to the isolation of the new compound artabotrene (1), two butenolides (2 and 3), and the tetracyclic triterpene polycarpol (4). Structure elucidation was determined on the basis of one and two-dimensional NMR, and absolute configuration of compounds 2-4 was verified by analysis of CD and optical rotation spectra. Two of the isolates, melodorinol (2) and acetylmelodorinol (3), were found to display antiproliferative activity against five different tumour cell lines with IC50 values ranging from 2.4 to 12 microM.

Antiproliferative cardenolides of an Elaeodendron sp. from the Madagascar rain forest(1).

Bioassay-guided fractionation of an ethanol extract obtained from the Madagascar plant Elaeodendron sp. led to the isolation of two new cardenolides, elaeodendrosides T and U (1 and 2). The structures of the new compounds were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1, 3, 4, and 5 showed significant antiproliferative activity against A2780 human ovarian cancer cells with IC50 values of 0.085, 0.019, 0.19, and 0.10 microM, respectively, while compounds 2 and 6 were less active.

Guttiferones K and L, antiproliferative compounds of Rheedia calcicola from the Madagascar rain forest.

Bioassay-guided fractionation of the ethanol extract obtained from the fruits of Rheedia calcicola led to the isolation of two new guttiferone analogues, guttiferones K (1) and L (16-hydroxyguttiferone K) (2). The structures of 1 and 2 were established on the basis of extensive interpretation of one- and two-dimensional NMR spectroscopic data. Both compounds were tested for their antiproliferative activity against the A2780 human ovarian cancer cell line.

Antiproliferative prenylated stilbenes and flavonoids from Macaranga alnifolia from the Madagascar rainforest.

Bioassay-guided fractionation of an extract of the fruit of Macaranga alnifolia from Madagascar led to the isolation of four new prenylated stilbenes, schweinfurthins E-H (1-4), and one new geranylated dihydroflavonol, alnifoliol (5). The known prenylated stilbene vedelianin (6) and the known geranylated flavonoids bonanniol A (7), diplacol (8), bonannione A (9), and diplacone (10) were also isolated. All 10 compounds were tested for antiproliferative activity in the A2780 human ovarian cancer cell line assay. Vedelianin (IC50 = 0.13 microM) exhibited the greatest activity among all isolates, while schweinfurthin E (IC50 = 0.26 microM) was the most potent of the new compounds.

Antiproliferative xanthones of Terminalia calcicola from the Madagascar rain forest.

A bioassay-guided fractionation of the EtOH extract of the Madagascan plant Terminalia calcicola led to the isolation of two new cytotoxic xanthones, termicalcicolanone A (1) and termicalcicolanone B (2). The structures of the new compounds were established on the basis of one- and two-dimensional NMR spectroscopic data. Both compounds showed modest antiproliferative activity toward the A2780 human ovarian cancer cell line.

Cytotoxic clerodane diterpenoids and their hydrolysis products from Casearia nigrescens from the rainforest of Madagascar.

Bioassay-guided fractionation of the cytotoxic leaf and flower extract of Casearia nigrescens led to the isolation of four new clerodane diterpenoids, designated caseanigrescens A-D (1-4). These compounds were subject to hydrolysis to dialdehydes when stored in CDCl3. The structures of compounds 1-4 were determined using 1D and 2D NMR spectroscopy. All four compounds showed moderate cytotoxicity to the A2780 human ovarian cancer cell line, with an IC50 range of 0.83-1.4 microM.

Cytotoxic triterpenoid saponins of Albizia gummifera from the Madagascar rain forest.

Bioassay-guided fractionation of an EtOH extract obtained from the roots of the Madagascan plant Albizia gummifera led to the isolation of three new cytotoxic oleanane-type triterpenoid saponins, gummiferaosides A-C (1-3). The structures of these new compounds were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1-3 showed cytotoxicity against the A2780 human ovarian cancer cell line with IC50 values of 0.8, 1.5, and 0.6 microg/mL, respectively.

Cytotoxic compounds of Physena madagascariensis from the Madagascar rain forest paragraph sign.

Two new flavanones, remangiflavanones D and E (1 and 2), were isolated from an extract of the twigs, leaves, and flowers of Physena madagascariensis together with three known flavanones, remangiflavanones A-C (3-5), and (E)-N-feruloyltyramine (6). The structures of the new compounds 1 and 2 were established on the basis of one-dimensional and two-dimensional NMR spectroscopic data interpretation. All compounds were evaluated for their cytotoxicity in the A2780 human ovarian cancer cell line. Compound 5 was the most active with an IC50 value of 2.5 microg mL-1.

Antiplasmodial activity of compounds from Sloanea rhodantha (Baker) Capuron var. rhodantha from the Madagascar rain forest.

Bioassay-directed separation of the butanol-soluble portion of an extract of Sloanea rhodantha (Baker) Capuron var. Rhodantha (Elaeocarpaceae) active against the drug-sensitive HB3 strain of Plasmodium falciparum led to the isolation of seven phenolic compounds, gallic acid (1), 3,5-di-O-galloylquinic acid (2), 1,6-di-O-galloyl glucopyranoside (3), 3,4,5-tri-O-galloylquinic acid (4), 1-O-eudesmoylquinic acid (5), 1,2,3,6-tetra-O-galloyl glucopyranoside (6), and 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-O-b-D-glucopyranoside (7). The structure of the new compound 5 was established on the basis of interpretation of its 1D and 2D NMR spectroscopic data. Compounds 2, 3, 4, 6, and 7 showed weak inhibitory activity against the drug-sensitive HB3 and the drug-resistant FCM29 strains of P. falciparum, with IC (50) values ranging from 8.0 - 43.0 and 16.1 - 93.0 microg/mL, respectively.

Cytotoxic and other compounds from Didymochlaena truncatula from the Madagascar rain forest.

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Didymochlaena truncatula led to the isolation of two cytotoxic alkaloids, camptothecin and 9-methoxycamptothecin. A second plant collection yielded three lignan derivatives, didymochlaenone A (1), didymochlaenone B (2), and (-)-wikstromol, one stilbene, (E)-3-methoxy-5-hydroxystilbene, and two stigmasterol derivatives, stigmast-4-en-3beta-ol and stigmast-4-en-3-one, but no camptothecins, and it is probable that a coding error led to a mistaken identification of the original extract. The structures of the new compounds 1 and 2 were established on the basis of extensive interpretation of one- and two-dimensional NMR spectroscopic data.