Frititaipaines A−O, undescribed cevanine-type isosteroidal alkaloids from the bulbs of Fritillaria taipaiensis and their anti-neuroinflammatory and AChE inhibitory activities

Fifteen undescribed cevanine-type isosteroidal alkaloids, frititaipaines A−O (1−15), and twelve known analogs (16−27) were isolated from the bulbs of Fritillaria taipaiensis. The structures of the previously undescribed compounds, including their absolute configurations, were fully elucidated based on spectroscopic, electronic circular dichroism spectra, and single-crystal X-ray diffraction data analysis. Compounds 3, 5, and 6 displayed significant inhibitory effects against lipopolysaccharide induced NO release in BV-2 microglial cells with IC₅₀ values of 6.3, 10.7, and 6.7 μM, respectively. All compounds showed no or weak acetylcholinesterase inhibitory activities as determined by the Ellman's method. Network pharmacological analysis and molecular docking results suggest that 3 may be able to treat Alzheimer's disease through pathways in cancer, PI3K-Akt signaling pathway, Rap1 signaling pathway, etc., as well as by binding PIK3CA, AKT1, SRC, PIK3R1, and ITGB1 targets.