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

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