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.

Antiproliferative Compounds from Ocotea macrocarpa from the Madagascar Dry Forest1.

Bioassay-directed fractionation of an antiproliferative ethanol extract of the roots of Ocotea macrocarpa (Lauraceae) afforded the new butanolide macrocarpolide A (1), and the two new secobutanolides macrocarpolides B (2) and C (3), together with the known butanolides linderanolide B (4) and isolinderanolide (5). The structure elucidation of all compounds was carried out based on NMR and mass spectroscopic data analyses. The absolute configurations of all compounds isolated were determined by comparison of their optical rotation values with those found in literature. Compounds 1-5 showed good antiproliferative activities against the A2780 ovarian cell line, with IC50 values of 2.57 ± 0.12 (1), 1.98 ± 0.23 (2), 1.67 ± 0.05 (3), 2.43 ± 0.41 (4), and 1.65 ± 0.44 µM (5), 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.

Bioactive compounds from Stuhlmannia moavi from the Madagascar dry forest.

Bioassay-directed fractionation of the leaf and root extracts of the antiproliferative Madagascar plant Stuhlmannia moavi afforded 6-acetyl-5,8-dihydroxy-2-methoxy-7-methyl-1,4-naphthoquinone (stuhlmoavin, 1) as the most active compound, with an IC50 value of 8.1 µM against the A2780 human ovarian cancer cell line, as well as the known homoisoflavonoid bonducellin (2) and the stilbenoids 3,4,5'-trihydroxy-3'-methoxy-trans-stilbene (3), piceatannol (4), resveratrol (5), rhapontigenin (6), and isorhapontigenin (7). The structure elucidation of all compounds was based on NMR and mass spectroscopic data, and the structure of 1 was confirmed by a single crystal X-ray analysis. Compounds 2-5 showed weak A2780 activities, with IC50 values of 10.6, 54.0, 41.0, and 74.0 µM, respectively. Compounds 1-3 also showed weak antimalarial activity against Plasmodium falciparum with IC50 values of 23, 26, and 27 µM, respectively.

Two antiproliferative triterpene saponins from Nematostylis anthophylla from the highlands of Central Madagascar.

Investigation of the endemic Madagascan plant Nematostylis anthophylla (Rubiaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the known triterpene saponin randianin (1), and the two new bioactive triterpene saponins 2"-O-acetylrandianin (2) and 6"-O-acetylrandianin (3). The structures of the two new compounds were elucidated based on analysis of their 1D- and 2D-NMR spectra, and mass spectrometric data. The three isolated triterpene saponins displayed moderate but selective antiproliferative activities, with IC(50) values of 1.2, 1.7, and 2.2 µM, respectively, against the A2780 ovarian cancer, but only weak inhibitions of the proliferation of A2058 melanoma and the H522 lung cancer cell lines.

Antiproliferative and antiplasmodial dimeric phloroglucinols from Mallotus oppositifolius from the Madagascar Dry Forest (1).

Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of Mallotus oppositifolius collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B (1) and C (2), together with the known mallotophenone (3). The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1D- and 2D-NMR spectra, mass spectrometry, and an X-ray crystal structure. Compounds 1 and 2 showed potent antimalarial activity against chloroquine-resistant Plasmodium falciparum, with IC50 values of 0.75 ± 0.30 and 0.14 ± 0.04 µM, while 3 was inactive in this assay. Compounds 1-3 also displayed strong antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 1.10 ± 0.05, 1.3 ± 0.1 and 6.3 ± 0.4 µM, respectively).

Antiproliferative acetogenins from a Uvaria sp. from the Madagascar dry forest.

Investigation of the endemic Madagascan plant Uvaria sp. for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of two new acetogenins. The structures of these two compounds were elucidated on the basis of analysis of their 1D and 2D NMR spectra, circular dichroism, and mass spectrometric data, together with chemical modification. The two acetogenins display weak antiproliferative activity against the A2780 ovarian cancer, the A2058 melanoma, and the H522 lung cancer cell lines.

Antiplasmodial and antiproliferative pseudoguaianolides of Athroisma proteiforme from the Madagascar Dry Forest.

Investigation of extracts from the plant Athroisma proteiforme (Humbert) Mattf. (Asteraceae) for antimalarial activity led to the isolation of the five new sesquiterpene lactones 1-5 together with centaureidin (6). The structures of the new compounds were deduced from analyses of physical and spectroscopic data, and the absolute configuration of compound 1 was confirmed by an X-ray crystallographic study. Athrolides C (3) and D (4) both showed antiplasmodial activities with IC50 values of 6.6 (3) and 7.2 µM (4) against the HB3 strain and 5.5 (3) and 4.2 µM (4) against the Dd2 strain of the malarial parasite Plasmodium falciparum. The isolates 1-6 also showed antiproliferative activity against A2780 human ovarian cancer cells, with IC50 values ranging from 0.4 to 2.5 µM.

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 of Cyphostemma greveana from a Madagascar dry forest.

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1ß,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1ß,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 µM (0.14 µg/ml) and 0.045 µg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance.

Isolation and synthesis of antiproliferative eupolauridine alkaloids of Ambavia gerrardii from the Madagascar Dry Forest.

Investigation of the Madagascan endemic plant Ambavia gerrardii for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the three new alkaloids 8-hydroxyeupolauridine (1), 9-methoxyeupolauridine 1-oxide (2), and 11-methoxysampangine (3) and the three known alkaloids 4-6. The structures of 1 and 2 were confirmed by synthesis. Compounds 3, 4, and 6 showed moderate to good antiproliferative activities, with IC50 values of 10.3, 3.5, and 0.60 µM, respectively, against the A2780 human ovarian cancer cell line and with IC50 values of 0.57, 1.77, and 0.58 µM, respectively, against the H460 human lung cancer cell line.

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.

Spatial distribution of dominant arboreal ants in a malagasy coastal rainforest: gaps and presence of an invasive species.

We conducted a survey along three belt transects located at increasing distances from the coast to determine whether a non-random arboreal ant assemblage, such as an ant mosaic, exists in the rainforest on the Masoala Peninsula, Madagascar. In most tropical rainforests, very populous colonies of territorially dominant arboreal ant species defend absolute territories distributed in a mosaic pattern. Among the 29 ant species recorded, only nine had colonies large enough to be considered potentially territorially dominant; the remaining species had smaller colonies and were considered non-dominant. Nevertheless, the null-model analyses used to examine the spatial structure of their assemblages did not reveal the existence of an ant mosaic. Inland, up to 44% of the trees were devoid of dominant arboreal ants, something not reported in other studies. While two Crematogaster species were not associated with one another, Brachymyrmex cordemoyi was positively associated with Technomyrmex albipes, which is considered an invasive species-a non-indigenous species that has an adverse ecological effect on the habitats it invades. The latter two species and Crematogaster ranavalonae were mutually exclusive. On the other hand, all of the trees in the coastal transect and at least 4 km of coast were occupied by T. albipes, and were interconnected by columns of workers. Technomyrmex albipes workers collected from different trees did not attack each other during confrontation tests, indicating that this species has formed a supercolony along the coast. Yet interspecific aggressiveness did occur between T. albipes and Crematogaster ranavalonae, a native species which is likely territorially dominant based on our intraspecific confrontation tests. These results suggest that the Masoala rainforest is threatened by a potential invasion by T. albipes, and that the penetration of this species further inland might be facilitated by the low density of native, territorially dominant arboreal ants normally able to limit its progression.

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.

A new species of Pandanaceae from northern Madagascar, Pandanus ankaranensis.

A new species, Pandanus ankaranensis Callm. & Laivao (Pandanaceae), is described from the karst region of Ankarana in northern Madagascar. It resembles P. grallatus B. C. Stone, another member of Pandanus sect. Mammillares H. St. John occurring in the area. The new taxon can be distinguished by its larger and wider leaves that are persistent on the branches, the stipe often lying on the rocks where plants grow, and its larger syncarps. Pandanus ankaranensis is classified as Vulnerable based on the IUCN Red List criteria.

Antiproliferative triterpenoid saponins of Dodonaea viscosa from the Madagascar dry forest.

Bioassay-guided fractionation of an EtOH extract obtained from the roots of the Madagascan plant Dodonaea viscosa led to the isolation of two new antiproliferative oleanane-type triterpenoid saponins, dodoneasides A and B (1 and 2). The structures of these two new compounds were elucidated using 1D and 2D NMR experiments and mass spectrometry. Compounds 1 and 2 showed antiproliferative activity against the A2780 human ovarian cancer cell line with IC(50) values of 0.79 and 0.70 muM, respectively.

Antiproliferative cardenolide glycosides of Elaeodendron alluaudianum from the Madagascar Rainforest.

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of Elaeodendron alluaudianum led to the isolation of two new cardenolide glycosides (1 and 2). The (1)H and (13)C NMR spectra of both compounds were fully assigned using a combination of 2D NMR experiments, including (1)H-(1)H COSY, HSQC, HMBC, and ROESY sequences. Both compounds 1 and 2 were tested against the A2780 human ovarian cancer cell line and the U937 human histiocytic lymphoma cell line assays, and showed significant antiproliferative activity with IC(50) values of 0.12 and 0.07 microM against the A2780 human ovarian cancer cell line, and 0.15 and 0.08 microM against the U937 human histiocytic lymphoma cell line, respectively.

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.