Qu_2025_Fitoterapia__106546

Ten new isosteroidal alkaloids, fritaipaines A - J (1-10), and six known congeners (11-16) were isolated from the bulbs of Fritillaria taipaiensis. The planar structure of these compounds as well as the absolute configuration, were fully elucidated based on spectroscopic and single-crystal X-ray diffraction data analysis and electronic circular dichroism (ECD) methods. Fritaipaines A (1) and B (2) are rare C(26) cevanine-type alkaloids having C-18 nor carbon skeleton. Fritaipaines C - F (3-6) are the first examples of jervine-type alkaloids featuring an inversed E/F ring moiety. The characteristic (13)C NMR data for judging E/F rings-inversion of jervine-type alkaloids were summarized. Compounds 5, 9, and 16 exhibited potent nitric oxide (NO) inhibitory activity in lipopolysaccharide (LPS) stimulated BV-2 cells with IC(50) values of 3.7 +/- 0.4, 10.3 +/- 1.1, and 6.9 +/- 0.7 microM, respectively. All compounds showed weak or no acetylcholinesterase (AChE) inhibition as determined by the Ellman's method. The results of network pharmacology experiments predicted that the anti-Alzheimer's disease (AD) effect of fritaipaine E (5) was related to 9 signaling pathways and 5 core targets, including SRC, PIK3CA, AKT1, EGFR, and IGF1R. Molecular docking simulations highlighted interactions between 5 and core targets, showing inhibitory effects on AD.