Biologically active franchetine-type diterpenoid alkaloids: Isolation, synthesis, anti-inflammatory, agalgesic activities, and molecular docking

In this study, four franchetine-type diterpenoid alkaloids (1-4) were isolated from Aconitum sinoaxillare, and fourteen diverse franchetine analogs (5-18) were synthesized. Compounds 1, 2, 7 and 16 exhibited stronger inhibitory effects on NO production when compared to celecoxib. Among them, compound 1 had the best inhibitory effect on iNOS and COX-2 inflammatory proteins. The in vitro studies displayed that the anti-inflammatory effect of the most active compound 1 was ascribed to the inhibition of the TLR4-MyD88/NF-κB/MAPKs signalling pathway. Consequently, this led to a inhibition in the expression of inflammatory factors or mediators including NO, ROS, TNF-α, IL-6, IL-1β, iNOS, and COX-2. Additionally, compound 1 had low toxicity (LD