Bioprospecting of UVB/UVA Absorbers in Fungi Associated with the Macroalga Phaeurus antarcticus Led to the Isolation of Isocoumarins and a Benzofuran with Photoprotective Potential.

Antarctic organisms are exposed to intense ultraviolet radiation (UVR) during austral summer, and although their photobiology remains poorly explored, their secondary metabolites play a key role in UV resistance, representing a promising source of novel photoprotective compounds. In this study, endophytic fungi associated with the seaweed Phaeurus antarcticus were screened for their ability to produce photoprotective metabolites. Four fungi were isolated and identified by ITS sequencing as Penicillium sp. (LMC 8102), Cladosporium sp. (LMC 8108), Rhinocladiella similis (LMC 8103), and Epicoccum sp. (LMC 8106). Among them, Penicillium sp. showed the highest UV absorbance and photostability. To enhance metabolite production, a culture media optimization was applied. Bioguided fractionation of the optimized extract led to the isolation of four compounds, 5,6,8-trihydroxy-4-(1-hydroxyethyl)-1H-isochromen-1-one (1), aspergillumarin A (2), sescandelin (3), and vermistatin (4). All compounds exhibited absorption bands within the UVB (280-320 nm) and UVA-II (320-340 nm) regions, particularly between 280-300 nm and 320-340 nm and were photostable. Compounds 2-4 maintained HaCaT cell viability above 79% under UVB exposure, while sescandelin (3) reduced UVA-induced ROS generation by 15% in HaCaT cells and 36.5% in reconstructed human skin. Photosafety evaluation using photoreactivity (OECD TG 495), phototoxicity (3T3 NRU PT, OECD TG 432), and ocular irritation (HET-CAM) assays demonstrated that compound 3 was nonphototoxic, whereas none of the evaluated compounds (2-4) exhibited photoreactivity. Compounds 3 and 4 did not induce ocular irritation in the HET-CAM assay. Overall, sescandelin (3) demonstrated the most promising photoprotective, antioxidant, and safety profile, supporting its potential application in topical sunscreen formulations.