(-)-6-epi-Artemisinin, a Natural Stereoisomer of (+)-Artemisinin in the Opposite Enantiomeric Series, from the Endemic Madagascar Plant Saldinia proboscidea, an Atypical Source.

Chemical and biological investigation of the Madagascar endemic plant Saldinia proboscidea led to the isolation of an isomer of artemisinin, (-)-6-epi-artemisinin (2). Its structure was elucidated using a combination of NMR and mass spectrometry. The absolute configuration was established by chemical syntheses of compound 2 as well as a new stereoisomer (3). The comparable bioactivities of artemisinin (1) and its isomer (-)-6-epi-artemisinin (2) revealed that this change in configuration was not critical to their biological properties. Bioactivity was assessed using an apoptosis induction assay, a SARS-CoV-2 inhibitor assay, and a haematin polymerization inhibitory activity (HPIA) assay. This is the first report of an artemisinin-related compound from a genus not belonging to Artemisia and it is the first isolation of an artemisinin-related natural product that is the opposite enantiomeric series relative to artemisinin from Artemisia annua.

Mode of action of diterpene and characterization of related metabolites from the soft coral, Xenia elongata.

Chemical and biological investigation of the cultured marine soft coral Xenia elongata led to the isolation of two new diterpenes (2, 3). Their structures were elucidated using a combination of NMR and mass spectrometry. Biological evaluations and assessments were determined using the specific apoptosis induction assay based on genetically engineered mammalian cell line D3 deficient in Bak and Bax and derived from a mouse epithelial cell. The diterpenes induce apoptosis in low micromolar concentrations. The results indicate that the previously isolated compound (1) affects cell in a manner similar to that of HSP90 and HDAC inhibitors and in a manner opposite of PI3 kinase/mTOR inhibitors. Compound (3) inhibits selectively HDAC6 in high micromolar concentrations.

Ammonificins C and D, hydroxyethylamine chromene derivatives from a cultured marine hydrothermal vent bacterium, Thermovibrio ammonificans.

Chemical and biological investigation of the cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine chromene derivatives, ammonificins C and D. Their structures were elucidated using combination of NMR and mass spectrometry. Absolute stereochemistry was ascertained by comparison of experimental and calculated CD spectra. Biological evaluation and assessment were determined using the patented ApopScreen cell-based screen for apoptosis-induction. Ammonificins C and D induce apoptosis in micromolar concentrations. To our knowledge, this finding is the first report of chemical compounds that induce apoptosis from the cultured deep-sea marine organism, hydrothermal vent bacterium, Thermovibrio ammonificans.

Bathymodiolamides A and B, ceramide derivatives from a deep-sea hydrothermal vent invertebrate mussel, Bathymodiolus thermophilus.

Two ceramide derivatives, bathymodiolamides A (1) and B (2), were isolated from the deep-sea hydrothermal vent invertebrate mussel Bathymodiolus thermophilus. The molecular structures of these compounds were determined using a combination of NMR spectroscopy, mass spectrometry, and chemical degradation. Biological activities were assessed in a ApopScreen cell-based screen for apoptosis induction and potential anticancer activity. To our knowledge, this is the first report of secondary metabolites from the marine hydrothermal vent mussel B. thermophilus.

Structural and synthetic investigations of tanikolide dimer, a SIRT2 selective inhibitor, and tanikolide seco-acid from the Madagascar marine cyanobacterium Lyngbya majuscula.

Tanikolide seco-acid 2 and tanikolide dimer 3, the latter a novel and selective SIRT2 inhibitor, were isolated from the Madagascar marine cyanobacterium Lyngbya majuscula. The structure of 2, isolated as the pure R enantiomer, was elucidated by X-ray experiment in conjunction with NMR and optical rotation data, whereas the depside molecular structure of 3 was initially thought to be a meso compound as established by NMR, MS, and chiral HPLC analyses. Subsequent total synthesis of the three tanikolide dimer stereoisomers 4, 5, and ent-5, followed by chiral GC-MS comparisons with the natural product, showed it to be exclusively the R,R-isomer 5. Tanikolide dimer 3 (= 5) inhibited SIRT2 with an IC(50) = 176 nM in one assay format and 2.4 microM in another. Stereochemical determination of symmetrical dimers such as compound 3 pose intriguing and subtle questions in structure elucidation and, as shown in the current work, are perhaps best answered in conjunction with total synthesis.

Ammonificins A and B, hydroxyethylamine chroman derivatives from a cultured marine hydrothermal vent bacterium, Thermovibrio ammonificans.

Two hydroxyethylamine chroman derivatives, ammonificins A (1) and B (2), were isolated from the marine hydrothermal vent bacterium Thermovibrio ammonificans. The molecular structures of these compounds were determined using a combination of NMR, mass spectrometry, and CD analyses. Biological activities were determined using an antimicrobial assay and the patented ApopScreen cell-based screen for apoptosis induction and potential anticancer activity. To our knowledge, this is the first report of secondary metabolites from the marine hydrothermal vent bacterium T. ammonificans.

Apoptosis-inducing galactolipids from a cultured marine diatom, Phaeodactylum tricornutum.

Two monogalactosyl diacylglycerols, 1 and 2, were isolated from the marine diatom Phaeodactylum tricornutum, using the patented ApopScreen cell-based screen for apoptosis-inducing, potential anticancer compounds. The molecular structures of the galactolipids were determined using a combination of NMR, mass spectrometry, and chemical degradation. The bioactivities were confirmed using a specific apoptosis induction assay based on genetically engineered mammalian cell lines with differential, defined capacities for apoptosis. The galactolipids induce apoptosis in micromolar concentrations. This is the first report of apoptosis induction by galactolipids.

Isolation of swinholide A and related glycosylated derivatives from two field collections of marine cyanobacteria.

[structure: see text] Chemical investigation of two field collections of marine cyanobacteria has led to the discovery of two new cytotoxic natural products, ankaraholides A (2) and B (3), along with the known compound swinholide A (1). Since swinholide-type compounds were previously localized to the heterotrophic bacteria of sponges, these findings raise intriguing questions about their true metabolic source.

Induction of apoptosis by diterpenes from the soft coral Xenia elongata.

Four new diterpenes ( 1- 4) were isolated from the soft coral Xenia elongata using a novel cell-based screen for apoptosis-inducing, potential anticancer compounds. The molecular structures of the diterpenes were determined using a combination of NMR and mass spectrometry. The bioactivities were confirmed using a specific apoptosis induction assay based on genetically engineered mammalian lines with differential, defined capacities for apoptosis. The diterpenes induce apoptosis in micromolar concentrations. This is the first report of apoptosis induction by marine diterpenes in xenicane skeletons.

DNA methyl transferase inhibiting halogenated monoterpenes from the Madagascar red marine alga Portieria hornemannii.

Three new halogenated monoterpenes, 2, 3, and 4, along with the known compounds halomon (1) and two analogues, 5 and 6, were isolated from the Madagascar red marine alga Portieria hornemannii. The structures of all three new compounds were determined by NMR spectroscopy in combination with mass spectrometric data analysis. Two of these monoterpenes (1 and 2) were low micromolar inhibitors of DNA methyl transferase-1.