Antimalarial 5,6-Dihydro-α-pyrones from Cryptocarya rigidifolia: Related Bicyclic Tetrahydro-α-Pyrones Are Artifacts

Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A–E (<b>1</b>–<b>5</b>) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F–K (<b>6</b>–<b>11</b>). The structure elucidations of all compounds were made on the basis of the interpretation of spectroscopic data and chemical derivatization, and the relative and absolute configurations were determined by NOESY, electronic circular dichroism (ECD), and ¹H NMR analysis of α-methoxyphenylacetyl (MPA) derivatives. The bicyclic tetrahydro-α-pyrone derivatives were identified as products of acid-catalyzed intramolecular Michael addition of the 5,6-dihydro-α-pyrones in the presence of silica gel. A structure–activity relationship study suggested that the presence of an α,β-unsaturated carbonyl moiety is not essential for potent antimalarial activity

Antiproliferative Acetogenins from a <i>Uvaria</i> sp. from the Madagascar Dry Forest

Investigation of the endemic Madagascan plant <i>Uvaria </i>sp<i>.</i> 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

Antiproliferative and Antiplasmodial Dimeric Phloroglucinols from <i>Mallotus oppositifolius</i> from the Madagascar Dry Forest

Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of <i>Mallotus oppositifolius</i> collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B (<b>1</b>) and C (<b>2</b>), together with the known mallotophenone (<b>3</b>). 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 <b>1</b> and <b>2</b> showed potent antimalarial activity against chloroquine-resistant <i>Plasmodium falciparum,</i> with IC₅₀ values of 0.75 ± 0.30 and 0.14 ± 0.04 μM, while <b>3</b> was inactive in this assay. Compounds <b>1</b>–<b>3</b> 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 Antiplasmodial Dimeric Phloroglucinols from <i>Mallotus oppositifolius</i> from the Madagascar Dry Forest

Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of <i>Mallotus oppositifolius</i> collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols mallotojaponins B (<b>1</b>) and C (<b>2</b>), together with the known mallotophenone (<b>3</b>). 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 <b>1</b> and <b>2</b> showed potent antimalarial activity against chloroquine-resistant <i>Plasmodium falciparum,</i> with IC₅₀ values of 0.75 ± 0.30 and 0.14 ± 0.04 μM, while <b>3</b> was inactive in this assay. Compounds <b>1</b>–<b>3</b> 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 Compounds from <i>Cleistanthus boivinianus</i> from the Madagascar Dry Forest

The two new lignans 3α-<i>O</i>-(β-d-glucopyranosyl)­desoxypodophyllotoxin (<b>1</b>) and 4-<i>O</i>-(β-d-glucopyranosyl)­dehydropodophyllotoxin (<b>2</b>) were isolated from <i>Cleistanthus boivinianus</i>, together with the known lignans deoxypicropodophyllotoxin (<b>3</b>), (±)-β-apopicropodophyllin (<b>4</b>), (−)-desoxypodophyllotoxin (<b>5</b>), (−)-yatein (<b>6</b>), and β-peltatin-5-<i>O</i>-β-d-glucopyranoside (<b>7</b>). The structures of all compounds were characterized by spectroscopic techniques. Compounds <b>1</b>, <b>4</b>, and <b>5</b> showed potent antiproliferative activities against the A2780 ovarian cancer cell line, with IC₅₀ values of 33.0 ± 3.6, 63.1 ± 6.7, and 230 ± 1 nM, respectively. Compounds <b>2</b> and <b>7</b> showed only modest A2780 activities, with IC₅₀ values of 2.1 ± 0.3 and 4.9 ± 0.1 μM, respectively, while compounds <b>3</b> and <b>6</b> had IC₅₀ values of >10 μM. Compound <b>1</b> also had potent antiproliferative activity against the HCT-116 human colon carcinoma cell line, with an IC₅₀ value of 20.5 nM, and compound <b>4</b> exhibited modest antiproliferative activity against the A2058 human caucasian metastatic melanoma and MES-SA human uterine sarcoma cell lines, with IC₅₀ values of 4.6 and 4.0 μM, respectively

Neolignans and Other Metabolites from <i>Ocotea cymosa</i> from the Madagascar Rain Forest and Their Biological Activities1

Ten new neolignans including the 6′-oxo-8.1′-lignans cymosalignans A (<b>1a</b>), B (<b>2</b>), and C (<b>3</b>), an 8.O.6′-neolignan (<b>4a</b>), ococymosin (<b>5a</b>), didymochlaenone C (<b>6a</b>), and the bicyclo[3.2.1]­octanoids <b>7</b>–<b>10</b> 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 <i>Ocotea cymosa</i>. The new 8.O.6′-neolignan <b>4a</b>, dihydrobenzofuranoid <b>5a</b>, and the bicyclo[3.2.1]­octanoid <b>7a</b> had in vitro activity against <i>Aedes aegypti</i>, while the new compounds <b>5a</b>, <b>7a</b>,<b> 8</b>, and <b>10a</b> and the known virolongin B (<b>4b</b>) and ocobullenone (<b>10b</b>) 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