Targeted Discovery of Sorbicillinoid Pigments with Anti-Inflammatory Activity from the Sponge-Derived Fungus Stagonospora sp. SYSU-MS7888 Using the PMG Strategy

An effective identification and discovery of fungal pigments is very important to illustrate the role of fungal pigments in the life process and conduce to the discovery of new bioactive and edible pigments. The phenotype combined with metabolomic and genomic (PMG) strategy led to the discovery and characterization of three new sorbicillinoid pigments, stasorbicillinoids A-C (1-3), and five known analogues (4-8) from the sponge-derived fungus Stagonospora sp. SYSU-MS7888. Their structures were elucidated by the application of spectroscopic methods (NMR, MS, UV, IR, and ECD) and modified Mosher's method. Compounds 1 and 2 featured novel naphthone nuclei linked by two alkyl side chains possibly undergoing inter- and intramolecular Michael reactions. Compounds 1-8 exhibited potent anti-inflammatory activity with IC50 values in the range of 3.56-22.8 μM. Furthermore, compound 2 inhibited the production of IL-1β, IL-6, and TNF-α in a dose-dependent manner. This study provides an effective strategy to accelerate the discovery of new fungal pigments and further exploration of their potential applications in different fields such as medicine and food industries.