New cyathane diterpenoids with neurotrophic and anti-neuroinflammatory activity from the bird's nest fungus Cyathus africanus

Eleven new cyathane diterpenoids, designated cyafricanins A-K (1 - 11), were isolated from the culture broth of the baisidiomycete Cyathus africanus (Nidulariaceae, Bird's nest fungi). Their structures were elucidated by comprehensive analysis of their NMR and HRESIMS data. Cyafricanins A (1) was found to possess an unusual 3,4-seco-carbon skeleton. All compounds were evaluated for their neurotrophic activity in PC-12 cells and antineuroinflammatory activity in BV2 microglia cells. All of the diterpenoids showed nerve growth factor induced neurite outgrowth-promoting activity at concentration of 20 mu M. Among them, cyafricanin B (2) and cyafricanin G (7) exhibited promising neurotrophic activity, and cyafricanin A (1) showed strong inhibitory effects on both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, molecular docking studies revealed that cyafricanin A (1) showed strong interactions with the iNOs protein in the active cavity.