Callyspongiolide, a Cytotoxic Macrolide from the Marine Sponge <i>Callyspongia</i> sp.

A novel macrolide, callyspongiolide, whose structure was determined by comprehensive analysis of the NMR and HRMS spectra, was isolated from the marine sponge <i>Callyspongia</i> sp. collected in Indonesia. The compound features a carbamate-substituted 14-membered macrocyclic lactone ring with a conjugated structurally unprecedented diene-ynic side chain terminating at a brominated benzene ring. Callyspongiolide showed strong cytotoxicity against human Jurkat J16 T and Ramos B lymphocytes

Cyclic Cystine-Bridged Peptides from the Marine Sponge <i>Clathria basilana</i> Induce Apoptosis in Tumor Cells and Depolarize the Bacterial Cytoplasmic Membrane

Investigation of the sponge <i>Clathria basilana</i> collected in Indonesia afforded five new peptides, including microcionamides C (<b>1</b>) and D (<b>2</b>), gombamides B (<b>4</b>), C (<b>5</b>), and D (<b>6</b>), and an unusual amide, (<i>E</i>)-2-amino-3-methyl-<i>N</i>-styrylbutanamide (<b>7</b>), along with 11 known compounds, among them microcionamide A (<b>3</b>). The structures of the new compounds were elucidated by one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configurations of the constituent amino acid residues in <b>1</b>–<b>7</b> were determined by Marfey’s analysis. Microcionamides A, C, and D (<b>1</b>–<b>3</b>) showed <i>in vitro</i> cytotoxicity against lymphoma (Ramos) and leukemia cell lines (HL-60, Nomo-1, Jurkat J16), as well as against a human ovarian carcinoma cell line (A2780) with IC₅₀ values ranging from 0.45 to 28 μM. Mechanistic studies showed that compounds <b>1</b>–<b>3</b> rapidly induce apoptotic cell death in Jurkat J16 and Ramos cells and that <b>1</b> and <b>2</b> potently block autophagy upon starvation conditions, thereby impairing pro-survival signaling of cancer cells. In addition, microcionamides C and A (<b>1</b> and <b>3</b>) inhibited bacterial growth of <i>Staphylococcus aureus</i> and <i>Enterococcus faecium</i> with minimal inhibitory concentrations between 6.2 and 12 μM. Mechanistic studies indicate dissipation of the bacterial membrane potential

Pro-Apoptotic and Immunostimulatory Tetrahydroxanthone Dimers from the Endophytic Fungus Phomopsis longicolla

Four tetrahydroxanthone dimers (<b>1</b>–<b>4</b>) and four biogenetically related monomers (<b>5</b>–<b>8</b>), including the new derivatives <b>4</b>–<b>6</b>, were isolated from the endophyte Phomopsis longicolla. The absolute configurations of <b>2</b>–<b>4</b> were established for the first time by TDDFT electronic circular dichroism calculations, and that of phomoxanthone A (<b>1</b>) was revised by X-ray crystallography. Phomoxanthone A (<b>1</b>) showed the strongest pro-apoptotic activity when tested against a panel of human cancer cell lines, including cisplatin-resistant cells, whereas it was up to 100-fold less active against healthy blood cells. It was also the most potent activator of murine T lymphocytes, NK cells, and macrophages, suggesting an activation of the immune system in parallel to its pro-apoptotic activity. This dual effect in combating cancer cells could help in fighting resistance during chemotherapy. Preliminary structure–activity studies of isolated compounds and derivatives obtained by semisynthesis (<b>9a</b>–<b>11</b>) hinted at the location of the biaryl axis and the presence of acetyl groups as important structural elements for the biological activity of the studied tetrahydroxanthones