Targeted Isolation of Photoactive Pigments from Mushrooms Yielded a Highly Potent New Photosensitizer: 7,7’-Biphyscion

Pigments of mushrooms are a fertile ground of inspiration: they spread across various chemical backbones, absorption ranges, and bioactivities. While looking from a photochemical perspective, we discovered a new bioactivity, i.e., photoactivity. We revealed that singlet oxygen production is a common theme in one group of webcaps (i.e., dermocyboid Cortinarii, formerly called Dermocybe). This photoactivity was explored by bioactivity-based molecular networking and photo-activity guided isolation. As a result, three photosensitizers based on anthraquinone structures were isolated. All three were photochemically characterized and (photo)cytotoxically tested. For one of the three, i.e. (-)-7,7’-biphyscion (1), a promising photoyield of fD= 20 % (lexc = 455 nm) and an excellent photocytotoxicity of approx. 64 nM against A549 lung cancer cell lines (lexc = 468 nm, 9.3 J/cm²) was found, while no effect was observed in the dark. Several molecular biological methods proved the harmlessness of 1 in the dark while showing that apoptosis is dose-dependent induced by 1 under irradiation. Therewith, 1 is a promising candidate for photodynamic therapy, while the photoactivity theme in the subgenus hints towards a yet unthought bioactivity in fungi: photoactivated defense.</p