Antiproliferative Trihydroxyalkylcyclohexenones from <i>Pleiogynium timoriense</i>

Investigation of a DCM extract of the bark of <i>Pleiogynium timoriense</i> from the former Merck collection of natural product extracts for antiproliferative activity indicated that it was active with an IC₅₀ value of 1.3 μg/mL against the A2780 ovarian cancer cell line. Bioassay-directed fractionation of this extract yielded the three new bioactive trihydroxyalkylcyclohexenones <b>1</b>–<b>3</b>. Their structures were determined by a combination of spectroscopic and chemical methods. Compounds <b>1</b>–<b>3</b> exhibited submicromolar antiproliferative activity against the A2780 human ovarian cancer cell line, with IC₅₀ values of 0.8, 0.7, and 0.8 μM, respectively

Antiproliferative Homoisoflavonoids and Bufatrienolides from <i>Urginea depressa</i>

Investigation of the South African plant <i>Urginea depressa</i> 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 (<b>1</b>–<b>6</b>), the two known bufatrienolides <b>7</b> and <b>9</b>, and the new bufatrienolides urginins B and C (<b>8</b> and <b>10</b>). 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 (<b>1</b>) had submicromolar activity against all three cell lines. The four bufatrienolides <b>7</b>–<b>10</b> had strong antiproliferative activity against the same cell line, with IC₅₀ values of 24.1, 11.2, 111, and 40.6 nM, respectively

Synthesis and Evaluation of Paclitaxel-Loaded Gold Nanoparticles for Tumor-Targeted Drug Delivery

The synthesis of a series of thiolated paclitaxel analogs is described as part of a novel nanomedicine program aimed at developing formulations of paclitaxel that will bind to gold nanoparticles for tumor targeted drug delivery. Preliminary evaluation of the new nanomedicine composed of 27 nm gold nanoparticles, tumor necrosis factor alpha (TNFα), thiolated polyethylene glycol (PEG-thiol), and one of several thiolated paclitaxel analogs is presented

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 <b>1</b>–<b>5</b> together with centaureidin (<b>6</b>). The structures of the new compounds were deduced from analyses of physical and spectroscopic data, and the absolute configuration of compound <b>1</b> was confirmed by an X-ray crystallographic study. Athrolides C (<b>3</b>) and D (<b>4</b>) both showed antiplasmodial activities with IC₅₀ values of 6.6 (<b>3</b>) and 7.2 μM (<b>4</b>) against the HB3 strain and 5.5 (<b>3</b>) and 4.2 μM (<b>4</b>) against the Dd2 strain of the malarial parasite Plasmodium falciparum. The isolates <b>1</b>–<b>6</b> also showed antiproliferative activity against A2780 human ovarian cancer cells, with IC₅₀ values ranging from 0.4 to 2.5 μM

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