Cyathane Diterpenes from Cultures of the Bird's Nest Fungus and Their Neurotrophic and Anti-neuroinflammatory Activities.

Six new cyathane diterpenoids, cyahookerins A-F (-), as well as nine known analogues (-), were isolated from the liquid culture of the basidiomycete . Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD), and the absolute configurations of compounds and were determined by single-crystal X-ray crystallography. Compounds and represent the first unusual cyathane acetals featuring a dioxolane ring. Compounds - displayed differential nerve growth factor-induced neurite outgrowth-promoting activity in PC-12 cells at concentrations of 10 μM. In addition, cyahookerin B (), cyathin E (), cyathin B (), and cyathin Q () showed significant nitric oxide production inhibition in Lipopolysaccharide (LPS)-activated BV-2 microglial cells with IC values of 12.0, 6.9, 10.9, and 9.1 μM, respectively. Similar binding modes of the four compounds were indicated by molecular-docking studies, and structure-activity relationships are discussed.