Cyathane Diterpenes from Cultures of the Bird's Nest Fungus Cyathus hookeri and Their Neurotrophic and Anti-neuroinflammatory Activities.
Dan TangYuan-Zhen XuWei-Wei WangZhi YangBo LiuMarc StadlerLing-Li LiuJin-Ming GaoPublished in: Journal of natural products (2019)
Six new cyathane diterpenoids, cyahookerins A-F (1-6), as well as nine known analogues (7-15), were isolated from the liquid culture of the basidiomycete Cyathus hookeri. Their structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD), and the absolute configurations of compounds 1 and 4 were determined by single-crystal X-ray crystallography. Compounds 1 and 2 represent the first unusual cyathane acetals featuring a dioxolane ring. Compounds 1-6 displayed differential nerve growth factor-induced neurite outgrowth-promoting activity in PC-12 cells at concentrations of 10 μM. In addition, cyahookerin B (2), cyathin E (9), cyathin B2 (12), and cyathin Q (13) showed significant nitric oxide production inhibition in Lipopolysaccharide (LPS)-activated BV-2 microglial cells with IC50 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.
Keyphrases
- molecular docking
- growth factor
- nitric oxide
- inflammatory response
- high resolution
- lps induced
- molecular dynamics simulations
- induced apoptosis
- lipopolysaccharide induced
- magnetic resonance
- high glucose
- hydrogen peroxide
- magnetic resonance imaging
- toll like receptor
- computed tomography
- endothelial cells
- cell proliferation
- spinal cord injury
- nitric oxide synthase