Aconicumines A-D, an advanced class of norditerpenoid alkaloids with an unprecedented N,O-diacetal motif from Aconitum taipeicum Hand.-Mazz., exhibit anti-inflammatory properties in vitro

Abstract

Aconicumines A-D, an advanced class of norditerpenoid alkaloids, and seven known alkaloids, were isolated from Aconitum taipaicum Hand.-Mazz. (Ranunculaceae). The structures of the previously undescribed compounds, including their absolute configurations, were fully elucidated based on spectroscopic and single-crystal X-ray diffraction data analysis. Aconicumines A-D exhibit interesting cage-like structure, characterised by an unprecedented N,O-diacetal moiety (C6-O-C19-N-C17-O-C7) that has not been previously observed in diterpenoid alkaloids. Possible biosynthetic pathways for aconicumines A-D were proposed. Aconitine, hypaconitine, and aconicumine A showed significant inhibition of nitric oxide production in RAW 264.7 macrophages induced by lipopolysaccharide with IC₅₀ values ranging from 4.1 to 19.7 μM compared to positive control (dexamethasone, IC₅₀ = 12.5 μM). Furthermore, the primary structure-activity relationships for aconicumines A-D were also represented.

Keywords: Aconitum taipaicum; Diacetal; Diterpenoid alkaloids; Hand.-Mazz.; NO inhibitory Activity; Ranunculaceae.