Alstiphyllanines I–O, ajmaline type alkaloids from Alstonia macrophylla showing vasorelaxant activity

Abstract: Seven new ajmaline type alkaloids, alstiphyllanines I–O (1–7) were isolated from the leaves of Alstonia macrophylla together with six related alkaloids (8–13). Structures and stereochemistry of 1–7 were fully elucidated and characterized by 2D NMR analysis. A series of alstiphyllanines I–O (1–7) as well as the known ajmaline type alkaloids (8–13) showed that they relaxed phenylephrine (PE)-induced contractions against rat aortic ring. Among them, vincamedine (10) showed potent vasorelaxant activity, which may be mediated through inhibition of Ca2+ influx through voltage-dependent Ca2+ channels (VDCs) and/or receptor-operated Ca2+ channels (ROCs) as well as partially mediated the NO release from endothelial cells. The presence of substituents at both N-1 and C-17 may be important to show vasorelaxation activity. [Copyright &y& Elsevier]