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.