Richard Randrianaivo

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 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 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.

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 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), 1β,6α‐dihydroxyeudesm‐4(15)‐ene (3), and (7R*)‐opposit‐4(15)‐ene‐1β,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 IC50 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.

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.

Sampling a Diverse Flora for Novel Biochemicals: An Analysis of NCI Collections from Madagascar

An analysis of the taxonomic composition of 6,496 samples of plants collected for the National Cancer Institute is conducted and the results are presented. The results show that collecting has been highly biased towards woody plant families, as these species are often abundant, they yield samples of multiple parts, and it is often easy to collect sufficient material for isolation of chemicals present in low concentration. Conversely, herbaceous plants that are small or grow in sparse populations are underrepresented in collections. Three of the ten generically most diverse families in Madagascar have not been sampled, and of these ten families, only Rubiaceae and Euphorbiaceae have had greater numbers of samples collected than predicted if collecting was random. The causes of this bias are discussed, and solutions to ensure that bioprospecting efforts gather samples reflective of the diversity present are presented.ZusammenfassungUne analyze de la composition taxonomique de 6496 échantillons recoltés pour le National Cancer Institute est conduite et les resultants obtenus montrent que la récolte a été foretment biaisée, tendant pour une forte proportion des families des plantes ligneuses don’t les espèces sont souvent abondantes, peuvent fournir plusieurs sortes d’échantillon et souvent permettent facilement de collecter suffisament des matérielles pour l’isolation des composes chimiques presents à faible concentration. Contrairement, les plantes herbacées que sont de petites tailles our qui poussent avec des populations clairsemées sont sous representées dans les collections. Trois parmi les dix families génériquement les plus diversifies n’ont pas été recoltées, et de ces dix families, seules les Rubiaceae el les Euphorbiaceae ont eu les plus grands nombres d’échantillons que prévus si la récolte a été fait au hazard. Les cause de cette disproportion sont discutées et les solutions pour assurer que les efforts de bioprospection rassemblent des échantillons reflétant la diversité présente sont presentées.

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 IC50 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.

A New Species of Pandanaceae from Northern Madagascar, Pandanus ankaranensis

Abstract 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 IUCN Red List criteria.