Antiproliferative Diterpenes from a Malleastrum sp. from the Madagascar dry forest.

An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (-)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 µM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum.

A Synthetic Butenolide Diterpene is now a Natural Product Isolated from Metaporana sericosepala, a Plant from the Madagascar Dry Forest.

Antiproliferative bioassay-guided fractionation of the ethanolic extract of the endemic Madagascan plant Metaporana sericosepala led to the first natural product isolation of a butenolide diterpene, which was synthesized during an anti-inflammatory study in 1988. The structure of the compound was elucidated as 3-homofarnesyl-4-hydroxybutenolide (1) by analysis of its spectroscopic data, including 1D- and 2D-NMR data and chemical evidence. The once synthetic compound can now also be considered as a natural product. Compound 1 had modest antiproliferative activity towards the A2780 ovarian cancer cell line,with an IC50 value of 8 µM.

Bioactive oleanane glycosides from Polyscias duplicata from the Madagascar dry forest.

As part of the International Cooperative Biodiversity Group (ICBG) program, in a search for antiproliferative compounds, an ethanol extract of Polyscias duplicata was investigated due to its antiproliferative activity against the A2780 human ovarian cell cancer line (IC50 6 µg/mL). Seven known oleanane glycosides, 3ß-[(α-L-arabinopyranosyl)oxy]-16α-hydroxyolean-12-en-28-oic acid (1, IC50 8 µM), 3ß-[(α-L-arabinopyranosyl)oxy]-16α,23-dihydroxyolean-12-en-18-oic acid (2, IC50 13 µM), 3ß-[(O-ß-D-glucopyranosyl-(t-->3)-α-L-arabinopyranosyl)oxy]-16α-hydroxyolean-12-en-28-oic acid (3, IC50 7 µM), 3ß-[(O-α-L-rhamnopyranosyl-(1-2)-α-L-arabinopyranosyl)oxy]-16α-hydroxyolean-12-en-28-oic acid (4, IC50 2.8 µM), 3ß-[(O-ß-D-glucopyranosyl-(l-->3)-α-L- arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (5, IC50 10 µM), ß-[(O-α-L-rhamnopyranosyl-(-1.2)-α-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (6, IC50 3.4 µM), and 3ß-[(α-L-arabinopyranosyl)oxy]-23-hydroxyolean-12-en-28-oic acid (7, IC50 3.4 µM) were isolated, and their structures determined using spectroscopic methods.

Antiproliferative and antimalarial sesquiterpene lactones from Piptocoma antillana from Puerto Rico.

Bioassay-directed fractionation of an antiproliferative ethanol extract of the leaves and twigs of Piptocoma antillana (Asteraceae) afforded two new goyazensolide-type sesquiterpene lactones named 5-O-methyl-5-epiisogoyazensolide (1) and 15-O-methylgoyazensolide (2), together with the known compounds 1-oxo-3,10-epoxy-8-(2-methylacr1 0-epoxy-8-(2-methylacryloxy)-l 5-acetoxygermacra-2,4, 11(1 3)-trien-6(12)-olide (3) and 5-epiisogoyazensolide (4). The structure elucidation of all compounds was carried out based on NMR and mass spectroscopic data analyses. The relative and absolute configurations of all the isolated compounds were determined from their CD and NOESY NMR spectra. Compounds 1-4 showed moderately potent antiproliferative activities against A2780 ovarian cancer cells, with IC50 values of 1.5 +0.5, 0.6 ± 0.3, 1.62 ± 0.05, and 1.56 ± 0.04 µM, respectively. They also displayed antimalarial activity against Plasmodiumfalciparum, with IC50 values of 6.2 05 22 ± 0.5, 2.2± 0.5, 8.0 ± 0.4, and 9.0 ± 0.6 µM, respectively.

A new bioactive diterpene glycoside from Molinaea retusa from the Madagascar dry forest.

In a continuing collaboration in a search for new antiproliferative compounds in Madagascar as part of an International Cooperative Biodiversity Group (ICBG), an ethanol extract of Molinaea retusa Radlk. (Sapindaceae) was investigated on the basis of its moderate antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 16 microg/mL). One new compound, 2", 3", 4", 6'-de-O-acetylcupacinoside (1, IC50 15.4 microM) and two known compounds, cupacinoside (2, IC50 9.5 microM) and 6-de-O-acetylcupacinoside (3, IC50 10.9 microM), were isolated by bioassay-directed fractionation using liquid-liquid partitioning, column chromatography, and HPLC. Compounds 2 and 3 also had moderate antiplasmodial activities, with IC50 values of 4.0 and 6.4 microM, respectively, against Plasmodium falciparum, Dd2 strain. The structures were determined using spectroscopic methods.

Isolation and synthesis of two antiproliferative calamenene-type sesquiterpenoids from Sterculia tavia from the Madagascar rain forest.

Investigation of the endemic Madagascan plant Sterculia taiva Baill. (Malvaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of two new bioactive calamenene-type sesquiterpenoids, named tavinin A (2) and epi-tavinin A (3) together with the known sesquiterpenoid mansonone G (1). The structures of the two new compounds were elucidated based on analysis of their 1D and 2D NMR spectra and mass spectrometric data, and were confirmed by de novo synthesis. The three isolated sesquiterpenoids (1-3) had modest antiproliferative activities against the A2780 ovarian cancer cell line, with IC(50) values of 10.2, 5.5 and 6.7 µM, respectively.

Two antiproliferative saponins of Tarenna grevei from the Madagascar dry forest [1].

Antiproliferative bioassay-guided fractionation of the ethanol extract of the endemic Malagasy Rubiaceous plant Tarenna grevei led to the isolation of two new antiproliferative oxygenated oleanane triterpene saponins. The structures of the two active compounds were elucidated as 23-hydroxylongispinogenin 3-O-beta-D-glucopyranoside (1) and longispinogenin 3-O-beta-D-glucopyranosyl (1 --> 2)-beta-D-glucopyranoside (3) by analyses of their spectral data including 1D- and 2D-NMR spectroscopy and chemical evidence. Compounds 1 and 3 displayed moderate antiproliferative activity against the A2780 ovarian cancer cell line with IC50 values of 7.6 and 4 microM, respectively.

Astrotricoumarin, an antiproliferative 4'-hydroxy-2',3'-dihydroprenylated methylcoumarin from an Astrotrichilia sp. from the Madagascar dry forest.

Bioassay guided fractionation of the ethanol extract of a new endemic species of the genus Astrotrichilia led to the isolation of the new antiproliferative 3-(4'-hydroxy-2',3'-dihydroprenyl)-4,6-dimethoxy-5-methylcoumarin, named astrotricoumarin (8) with an IC50 value of 6.8 microM against the A2780 cell line. The structure of compound 8 was elucidated on the basis of its physical and spectroscopic data, including extensive 1D- and 2D-NMR analysis.

Antiproliferative compounds from Pongamiopsis pervilleana from the Madagascar Dry Forest.

Bioassay-guided fractionation of an ethanol extract of the roots of the endemic Malagasy plant Pongamiopsis pervilleana led to the isolation of the three new compounds (2'R)-4'-hydroxyemoroidocarpan (1), pongavilleanine (3), and epipervilline (4) together with two known compounds, identified as emoroidocarpan (2) and rotenolone (5). The structures of all compounds were determined by physical, chemical, and spectroscopic evidence. The stereochemistry at C-2' of the previously reported compound emoroidocarpan was determined to be R by the observation of a negative Cotton effect at 474 nm in the CD spectrum of its osmate ester derivative. Compounds 2-5 displayed moderate antiproliferative activity against the A2780 human ovarian cancer cell line, and rotenolone also showed micromolar antiproliferative activity toward the breast cancer BT-549, prostate cancer DU 145, NSCLC NCI-H460, and colon cancer HCC-2998 cell lines.

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.

Euphane triterpenoids of Cassipourea lanceolata from the Madagascar rainforest.

Fractionation of an ethanol extract of a Madagascar collection of the leaves and fruit of Cassipourea lanceolata Tul. led to the isolation of three euphane triterpenoids 1-3. The (1)H and (13)C NMR spectra of all compounds were fully assigned using a combination of 2D NMR experiments, including COSY, TOCSY, HSQC (HMQC), HMBC and ROESY sequences. The three compounds showed weak antiproliferative activities against the A2780 human ovarian cancer cell line, with IC(50) values of 25, 25 and 32 microM, respectively.

Saponins and a lignan derivative of Terminalia tropophylla from the Madagascar Dry Forest.

A study of an EtOH extract obtained from the roots of the Madagascan plant Terminalia tropophylla H. Perrier (Combretaceae) led to isolation of the oleanane-type triterpenoid saponin 1, the lignan derivative 2, and the two known saponins arjunglucoside I (3) and sericoside (4). The structures of compounds 1 (terminaliaside A) and 2 (4'-O-cinnamoyl cleomiscosin A) were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compound 1 showed antiproliferative activity against the A2780 human ovarian cancer cell line with an IC(50) value of 1.2 microM.

Antiproliferative and antimalarial anthraquinones of Scutia myrtina from the Madagascar forest.

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of the bark of Scutia myrtina led to the isolation of three new anthrone-anthraquinones, scutianthraquinones A, B and C (1-3), one new bisanthrone-anthraquinone, scutianthraquinone D (4), and the known anthraquinone, aloesaponarin I (5). The structures of all compounds were determined using a combination of 1D and 2D NMR experiments, including COSY, TOCSY, HSQC, HMBC, and ROESY sequences, and mass spectrometry. All the isolated compounds were tested against the A2780 human ovarian cancer cell line for antiproliferative activities, and against the chloroquine-resistant Plasmodium falciparum strains Dd2 and FCM29 for antiplasmodial activities. Compounds 1, 2 and 4 showed weak antiproliferative activities against the A2780 ovarian cancer cell line, while compounds 1-4 exhibited moderate antiplasmodial activities against P. falciparum Dd2 and compounds 1, 2, and 4 exhibited moderate antiplasmodial activities against P. falciparum FCM29.

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 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.