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

Abstract

<p><a>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 (<b>1</b>), a promising photoyield of </a>f<sub>D</sub>= 20 % (l<sub>exc</sub> = 455 nm) and an excellent photocytotoxicity of approx. 64 nM against A549 lung cancer cell lines (l<sub>exc</sub> = 468 nm, 9.3 J/cm²) was found, while no effect was observed in the dark. Several molecular biological methods proved the harmlessness of <b>1</b> in the dark while showing that apoptosis is dose-dependent induced by <b>1</b> under irradiation. Therewith, <b>1</b> 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>

Highlighting the Phototherapeutical Potential of Fungal Pigments in Various Fruiting Body Extracts with Informed Feature-Based Molecular Networking

“…In 2013, Li and colleagues were able to isolate two new anthraquinone dimers from the fruiting bodies of B. inquinans , namely bulgareone A and bulgareone B [ 71 ]. With the discovery of several photosensitizing dimeric anthraquinones with promising anticancer, antiparasitic, or even antiviral activity, such as 7,7′-biphyscion from C. uliginosus [ 10 ] and 5,5′-bisoranjidiol from Heterophyllaeae lycioides [ 72 , 73 ], the investigation of the bulgareones with respect to a photodynamic effect could be of great interest. Thus, taking together the high levels of singlet oxygen production and the considerable light-dependent photocytotoxicity of the extracts of B. inquinans and D. concentrica , their thorough myco- and photochemical analysis could yield highly active compounds with extraordinary value for the field of photodynamic therapy.…”

“…Fortyeight different species were selected to cover most of the described pigment types. Second, dried and ground fruiting bodies were extracted and subjected to untargeted UHPLC-HRMS/MS metabolite profiling together with previously isolated fungal photosensitizers [10,12]. The obtained data was used to generate a FBMN [25].…”

“…Several Cortinarius species have already been studied by us in terms of their phototoxic properties, which even led to the isolation and structure elucidation of novel photosensitizers (e.g., 7,7′-biphyscion, dermolutein, and emodin-1-Oβ-D-glucopyranoside) [9,10,12].…”

“…For example, anticancer activities (e.g., ganoderic acid T from Ganoderma lucidum [ 7 ]) or hallucinogenic effects (e.g., psilocybin from Psilocybe mexicana [ 8 ]) are reported. Recent studies on the genus Cortinarius have even led to the discovery of an activity previously unknown for basidiomycetes: photoactivity [ 9 , 10 ].…”