Peggy J. Brodie

Antiproliferative cassane diterpenoids of Cordyla madagascariensis ssp. madagascariensis from the Madagascar rainforest.

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of the fruits of Cordyla madagascariensis ssp. madagascariensis led to the isolation of the four new cassane diterpenoids 1-4. The 1H and 13C NMR spectra of all compounds were fully assigned using a combination of 2D NMR experiments, including COSY, HSQC, HMBC, and ROESY sequences. All of the isolates were tested against the A2780 human ovarian cancer cell line, and compounds 1 and 2 showed mild antiproliferative activity with IC50 values of 10 and 36 microM, respectively.

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 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.

Four Diphenylpropanes and a Cycloheptadibenzofuran from Bussea sakalava from the Madagascar Dry Forest

Investigation of the endemic Malagasy plant Bussea sakalava for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the four new diphenylpropanes 1-4 and the new cycloheptadibenzofuran 5; compound 5 has a previously unreported natural product skeleton. The structure elucidation of these compounds was based on the analysis of their 1D and 2D NMR and mass spectroscopic data. Compounds 1-5 were tested for antiproliferative activity against the A2780 human ovarian cancer cell line.

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 bistramides from Trididemnum cyclops from Madagascar (1).

Bioassay-guided fractionation of a marine extract from Trididemnum cyclops afforded the new lipopeptide 39-oxobistramide K (1) and the known bistramides A (2) and D (3). Structure elucidation of 1 was carried out by analysis of one- and two-dimensional NMR spectroscopy and HRMS data. Bistramides have been reported to exhibit antiproliferative activity in the nanomolar range against a number of tumor cell lines in vitro and in vivo. The isolate 1 was tested for antiproliferative activity against the A2780 cell line and exhibited an IC(50) value of 0.34 microM.

Design and Synthesis of C6-C8 Bridged Epothilone A

A conformationally restrained epothilone A analogue (3) with a short bridge between methyl groups at C6 and C8 was designed and synthesized. Preliminary biological evaluation indicates 3 to be only weakly active (IC50 = 8.5 microM) against the A2780 human ovarian cancer cell line.

Antiproliferative Homoisoflavonoids and Bufatrienolides from Urginea depressa

Investigation of the South African plant Urginea depressa Baker (Asparagaceae Juss.) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the six new homoisoflavonoids urgineanins A-F (1-6), the two known bufatrienolides 7 and 9, and the new bufatrienolides urginins B and C (8 and 10). Structures were elucidated based on analysis of their 1D and 2D NMR spectra, electronic circular dichroism, and mass spectrometric data. Five of the six new homoisoflavonoids had good antiproliferative activity against the A2780 ovarian cancer, A2058 melanoma, and H522-T1 human non-small-cell lung cancer cells, and urgineanin A (1) had submicromolar activity against all three cell lines. The four bufatrienolides 7-10 had strong antiproliferative activity against the same cell line, with IC50 values of 24.1, 11.2, 111, and 40.6 nM, 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.

Cardenolides of Leptadenia madagascariensis from the Madagascar dry forest.

Investigation of the endemic Madagascar plant Leptadenia madagascariensis Decne. (Apocynaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the four new cardenolides 1-4. The structure elucidations of these compounds were based on analyzes of their 1D and 2D NMR spectra and mass spectrometric data. The cardenolides were strongly antiproliferative to the A2780 ovarian cancer cell line, with IC(50) values of 0.18, 0.21, 0.17, and 0.29μM line, and to the H460 human lung cancer cell line, with IC(50) values of 0.16, 0.68, 0.37, and 0.48μM, respectively.