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

Additional file 1: Figure S1. of Transient IKK2 activation in astrocytes initiates selective non-cell-autonomous neurodegeneration

Additional phenotypic characterization of IKK2-CA and IKK2-DN mice. Figure S2. Additional immune cell markers and proinflammatory genes characterizing IKK2-CA-induced cerebellar neuroinflammation. Figure S3. Neuroinflammation is also found in other brain regions, but neurodegeneration is restricted to the cerebellum. Figure S4. Expression kinetics of inflammatory mediators upon transgene inactivation in IKK2-CA mice. Figure S5. The IKK2-CA transgene is not expressed in Purkinje cells or microglia. Figure S6. Local microglia activation is not sufficient to drive Purkinje cell degeneration. Figure S7. Characterisation of Bergmann glia specific expression of the IKK2-CA-IRES-GFP transgene in the IKK2-CASept4 model. Figure S8. Characterization of glutamate transporter expression in response to astroglial IKK2 activation. (PDF 20468 kb