Novel Phenanthraquinone Derivative from Antarctic Lichen Umbilicaria antarctica Exhibits Apoptotic Activity in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is one of the most challenging malignancies in modern drug development, as its poor prognosis and limited therapeutic options create an urgent demand for innovative treatments. To address this, Antarctic lichensknown for their diverse pharmacological activities, including anticancer, antioxidant, antimicrobial, and anti-inflammatory effectswere selected as a natural source for potential lead compounds. Extensive chemical analysis of Umbilicaria antarctica (L.) Ach., a lichen species prevalent on Antarctic rocky terrains, successfully led to the isolation of new compounds, carboxygyrophoric acid (1) and umbiliquinone (2). The chemical structures of 1 and 2 were determined through extensive spectroscopic methods and ECD calculations. All compounds (1-15) were evaluated for their cytotoxicity against SK-OV-3, MDA-MB-231, and A549 cancer cell lines. The new compound, umbiliquinone (2), exhibited statistically significant cytotoxicity in all three cell lines, notably including the TNBC cell lines MDA-MB-231. It exhibited IC50 values between 28 and 57 μM across these cell lines. Combined with the observed activity of compounds 9, 11, 13, 14, and 15, these findings strengthen the evidence for their development as potential agents against TNBC. Molecular dynamics (MD) simulations were further conducted to investigate the interactions between compounds 2 and 9 and Bcl-2, an antiapoptotic protein, to gain mechanistic insight into their potential proapoptotic effects.