Talamangins A-C, Immunosuppressive and Anti-inflammatory Nitrogenated Azaphilone Hybrids from Talaromyces mangshanicus SB17.

Three unprecedented nitrogenated azaphilone hybrids, talamangins A-C (1-3), were isolated from the endophytic fungus Talaromyces mangshanicus SB17. Their structures, along with their absolute configurations, were determined by extensive spectroscopic data analysis and single-crystal X-ray diffraction. Compounds 1-3 represent the first examples of nitrogenated azaphilone hybrids, distinguished by a novel fused scaffold formed through the angular fusion of nitrogenated azaphilone and a benzophenone unit, with the azaphilone fragment featuring a pyridine ring. Plausible biosynthetic pathways for 1-3 are proposed. Compounds 1-3 exhibit potent immunosuppressive activities against concanavalin A (ConA)-induced T cell proliferation, with IC₅₀ values of 13.0, 14.3, and 24.1 μM, respectively, as well as against lipopolysaccharide (LPS)-induced B cell proliferation, with IC₅₀ values of 14.5, 18.5, and 19.2 μM, respectively. Additionally, compounds 1-3 inhibit nitric oxide production in LPS-induced RAW264.7 cells, with IC₅₀ values of 6.2, 9.4, and 10.5 μM, respectively.