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Papers of the Week


Papers: 28 Sep 2024 - 4 Oct 2024


2024 Sep 21


Bioorg Chem


39332071


153

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

Authors

Xiao Y, Chang Y, Liu YY, Li TT, Qu WR, Yuan C, Chen L, Huang S, Zhou XL

Abstract

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 > 20 mg/kg) in mice, and it had notable analgesic effects on acetic acid-induced visceral pain (ED = 2.15 ± 0.07 mg/kg). Moreover, compound 1 exhibited a distinct reduction in the Na1.7 and Na1.8 channel currents during both resting and half-inactivated states at 50 μM. The present study enriches the pharmacological activities of franchetine derivatives and provides valuable insights for the development of novel anti-inflammatory and analgesic agents.