Cyathstrines A-K, Structurally Diverse Polycyclic Polyoxygenated Cyathane Diterpenoid Xylosides with Antibacterial...

A chemical investigation of the basidiomycete Cyathus striatus led to the isolation of 17 polyoxygenated cyathane diterpenoid xylosides, cyathstrines A-K (1-17), including 11 new ones sharing five distinct ring skeletons, two sesquiterpenoids (18 and 19), and two lupane triterpenoids (20 and 21), as well as three sterols (22-24), based on the OSMAC (One Strain-Many Compounds) strategy. Among them, compound 5 represents the first example of cyathane diterpenoids with an undescribed 5/6/7/6/5/6/6-fused ring skeleton incorporating an extra 2H-pyran moiety, and compound 7 bears an unconventional 9/7/6/5/6-fused pentacyclic ring skeleton. The structures of these compounds were elucidated by means of NMR spectroscopic analyses, HRESIMS and ECD calculations. Compounds 7 and 9 exhibited moderate antibacterial effects against six human pathogenic bacteria, with MIC values ranging from 8 to 32 μg/mL. Meanwhile, compound 8 showed significant neuroprotective activity at 20 μM, with cell viability improved to 82.4% from the MPP⁺-treated cell viability of 51.20%, which was comparable to the positive control. Additionally, compounds 3, 13, 15, and 17 demonstrated notable neuroprotective effects, with cell viabilities of more than 70%. These findings expanded the chemical space of cyathane diterpenoids and provided the new template molecules for the development of anti-infective and neuroprotective drugs.