Phenanthrene Monomers and Dimers from Juncus tenuis with Antiproliferative Activity and Synergistic Effect with Doxorubicin Against Human Colon Cancer Cell Lines

Continuing our search for bioactive compounds in species from the Juncaceae family, we investigated <i>Juncus tenuis</i>. The structures of five previously undescribed phenanthrenes-tenuins A-E (<b>1</b>-<b>5</b>)-and 14 known phenanthrenes (<b>6</b>-<b>19</b>), along with other components, were isolated and characterized using nuclear magnetic resonance and high-resolution mass spectrometry measurements. The antiproliferative activity of all of the isolated phenanthrenes was evaluated against the human colorectal adenocarcinoma cell lines COLO 205 (doxorubicin-sensitive) and COLO 320 (doxorubicin-resistant), as well as a non-tumorigenic human fibroblast cell line (CCD-19Lu), using the MTT viability assay. Diphenanthrenes <b>4</b>, <b>5</b>, and <b>19</b> showed the most potent antiproliferative effects, with IC₅₀ values ranging from 7.60 to 17.32 μM; however, these compounds lacked selectivity toward cancer cells. To explore potential chemosensitizing properties, the synergistic effects of the phenanthrenes with the anticancer drug doxorubicin were also examined in the COLO 320 cells. Notably, compound <b>2</b> exhibited very strong synergism (CI = 0.021), indicating a highly potent interaction. These findings highlight <i>J. tenuis</i> as a valuable source of phenanthrenes and demonstrate the synergistic anticancer potential of natural phenanthrenes with doxorubicin, offering promising prospects for overcoming multidrug resistance in colorectal cancer therapy.