Dimeric tetrahydroxanthones from the lichen Usnea aciculifera

Area of Science:

• Natural Product Chemistry
• Lichenology
• Medicinal Chemistry

Background:

• Lichens are a symbiotic association of fungi and algae, known to produce diverse secondary metabolites.
• Usnea species are a rich source of bioactive compounds, including xanthones.
• Tetrahydroxanthones represent a less explored class of lichen metabolites.

Purpose of the Study:

• To isolate and characterize novel heterodimeric tetrahydroxanthones from the lichen *Usnea aciculifera*.
• To elucidate the structures and absolute configurations of the isolated compounds.
• To evaluate the cytotoxic potential of the isolated compounds against human colorectal cancer cells.

Main Methods:

• Isolation of compounds using chromatographic techniques.
• Structure elucidation through comprehensive spectroscopic analyses (1D, 2D NMR, HRESIMS).
• Determination of absolute configurations via electronic circular dichroism (ECD) and single-crystal X-ray crystallography.
• Cytotoxicity assays using HT-29 human colorectal cancer cell line.

Main Results:

• Four unusual heterodimeric tetrahydroxanthones, named usneaxanthones A-D (1-4), were successfully isolated.
• The structures and absolute configurations, including central and axial chiralities, were unambiguously determined.
• Compounds 1, 2, and 4 exhibited cytotoxic effects against HT-29 cells.
• Usneaxanthone D (4) displayed potent cytotoxicity with an IC₅₀ value of 2.41 μM.

Conclusions:

• The study reports the discovery of four novel tetrahydroxanthones from *Usnea aciculifera*.
• The findings highlight the potential of lichen-derived compounds as sources for anticancer drug discovery.
• Usneaxanthone D shows promising cytotoxic activity warranting further investigation for colorectal cancer therapy.