Cytotoxic Barrigenol-like Triterpenoids from an Extract of <i>Cyrilla racemiflora</i> Housed in a Repository

Two new [(+)-cyrillins A (<b>1</b>) and B (<b>2</b>)] and four known barrigenol-like triterpenoids (<b>3</b>–<b>6</b>), along with betulinic acid and (+)-3β-<i>O</i>-<i>trans</i>-feruloylbetulinic acid, were isolated from a sample-restricted CH₂Cl₂-soluble extract of the bark of <i>Cyrilla racemiflora</i>, collected in Dominica. The structures of the new compounds were elucidated by interpretation of their spectroscopic data, and the absolute configuration of the cyclic 1,2-diol unit of (+)-cyrillin A (<b>1</b>) was ascertained by analysis of the electronic circular dichroism (ECD) spectrum induced with [Mo₂(OAc)₄]. In the case of (+)-cyrillin B (<b>2</b>), which was found to contain a diangeloylated glucose residue, the structure proposed was supported by analysis of its MS² and MS³ spectra. All compounds isolated were evaluated for their cytotoxicity against HT-29 human colon cancer cells, and the known compound, (+)-barringtogenol B (<b>3</b>), was found to be the most potent, exhibiting an IC₅₀ value of 1.7 μM. This compound also showed inhibitory activity toward the CCD-112CoN human normal colon cell line, with an IC₅₀ value of 5.9 μM, indicating a lack of cytotoxic selectivity

Antiplasmodial Diterpenoids and a Benzotropolone from <i>Petradoria pumila</i>

An extract of <i>Petradoria pumila</i> from the Natural Products Discovery Institute was found to have moderate antiplasmodial activity, with an IC₅₀ value between 5 and 10 μg/mL. The four new diterpenoids petradoriolides A–D (<b>1</b>–<b>4</b>), the new benzotropolone petradoriolone (<b>5</b>), and the two known lignans <b>6</b> and <b>7</b> were isolated after bioassay-directed fractionation. The structures and stereochemistries of the new compounds were determined by interpretation of NMR spectroscopy, mass spectrometry, and ECD spectra. Among these compounds, petradoriolide C (<b>3</b>) displayed the most potent antiplasmodial activity, with an IC₅₀ value of 7.3 μM

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

Constituents of an Extract of <i>Cryptocarya rubra</i> Housed in a Repository with Cytotoxic and Glucose Transport Inhibitory Effects

A new alkylated chalcone (<b>1</b>), a new 1,16-hexadecanediol diester (<b>2</b>), and eight known compounds were isolated from a dichloromethane-soluble repository extract of the leaves and twigs of <i>Cryptocarya rubra</i> collected in Hawaii. The structures of the new compounds were determined by interpretation of their spectroscopic data, and the absolute configurations of the two known cryptocaryanone-type flavonoid dimers, (+)-bicaryanone A (<b>3</b>) and (+)-chalcocaryanone C (<b>4</b>), were ascertained by analysis of their electronic circular dichroism and NOESY NMR spectra. All compounds isolated were evaluated against HT-29 human colon cancer cells, and, of these, (+)-cryptocaryone (<b>5</b>) was found to be potently cytotoxic toward this cancer cell line, with an IC₅₀ value of 0.32 μM. This compound also exhibited glucose transport inhibitory activity when tested in a glucose uptake assay

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

Antiplasmodial Chromanes and Chromenes from the Monotypic Plant Species <i>Koeberlinia spinosa</i>

Nine new compounds containing either a chromane or chromene ring moiety were isolated from the monotypic plant <i>Koeberlinia spinosa</i>. Compounds <b>1</b>–<b>4</b> are chromanes with all possible <i>E</i> and <i>Z</i> isomers of the isoprenoid side chain, with compound <b>5</b> a methylated derivative of <b>1</b>. Compounds <b>6</b> and <b>7</b> were assigned as diastereomeric cyclized derivatives of <b>2</b> and were probably artifacts formed during the extraction or the isolation processes. Compounds <b>8</b> and <b>9</b> were characterized as new chromenes. Structure elucidation of <b>1</b>–<b>9</b> was conducted via 1D and 2D NMR spectroscopic data interpretation, and absolute configurations were determined by ECD spectroscopic analysis. Compounds <b>2</b>, <b>5</b>, <b>6</b>, and <b>7</b> had weak antiplasmodial activity, while none of the compounds exhibited antiproliferative activity. The isolation, structure elucidation, and biological evaluation of these compounds are presented

Isolation, Structure Elucidation, and Antibacterial Activity of Methiosetin, a Tetramic Acid from a Tropical Sooty Mold (<i>Capnodium</i> sp.)

Drug-resistant bacteria continue to make many existing antibiotic classes ineffective. In order to avoid a future epidemic from drug-resistant bacterial infections, new antibiotics with new modes of action are needed. In an antibiotic screening program for new drug leads with new modes of action using antisense <i>Staphylococcus aureus</i> Fitness Test screening, we discovered a new tetramic acid, methiosetin, from a tropical sooty mold, <i>Capnodium</i> sp. The fungus also produced epicorazine A, a known antibiotic. The structure and relative configuration of methiosetin was elucidated by 2D NMR and ESIMS techniques. Methiosetin and epicorazine A showed weak to modest antibacterial activity against <i>S. aureus</i> and <i>Haemophilus influenzae</i>. The isolation, structure elucidation, and antibacterial activity of both compounds are described