Cytotoxic and Protein Kinase Inhibiting Nakijiquinones and Nakijiquinols from the Sponge <i>Dactylospongia metachromia</i>

Chemical investigation of the sponge <i>Dactylospongia metachromia</i> afforded five new sesquiterpene aminoquinones (<b>1</b>–<b>5</b>), two new sesquiterpene benzoxazoles (<b>6</b> and <b>7</b>), the known analogue 18-hydroxy-5-<i>epi</i>-hyrtiophenol (<b>8</b>), and a known glycerolipid. The structures of all compounds were unambiguously elucidated by one- and two-dimensional NMR and by MS analyses, as well as by comparison with the literature. Compounds <b>1</b>–<b>5</b> showed potent cytotoxicity against the mouse lymphoma cell line L5178Y with IC₅₀ values ranging from 1.1 to 3.7 μM. When tested <i>in vitro</i> for their inhibitory potential against 16 different protein kinases, compounds <b>5</b>, <b>6</b>, and <b>8</b> exhibited the strongest inhibitory activity against ALK, FAK, IGF1-R, SRC, VEGF-R2, Aurora-B, MET wt, and NEK6 kinases (IC₅₀ 0.97–8.62 μM)

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