Diterpene Alkaloids fromAconitum anthoraand Assessment of the hERG-Inhibiting Ability ofAconitumAlkaloids

Abstract

A new norditerpene alkaloid, 10-hydroxy-8- O-methyltalatizamine (1), was isolated from the whole plant of ACONITUM ANTHORA L. besides the known isotalatizidine (2) and hetisinone (3). The structures were determined by means of HR-ESI-MS, 1D and 2D NMR spectroscopy, including ¹H-¹H COSY, NOESY, HSQC and HMBC experiments, resulting in complete ¹H and ¹³C chemical shift assignments for 1- 3, and revision of some earlier ¹³C-NMR data. The effects of the isolated compounds, together with twenty-one other ACONITUM alkaloids with different skeletal types and substitution patterns, on hERG channels were studied by the whole-cell patch clamp technique, using the QPatch-16 automated patch clamp system. At 10 µM, aconitine, 14-benzoylaconine 8- O-palmitate, songoramine, gigactonine and neolinine demonstrated significant hERG K+ channel inhibition; all other compounds exerted only low (6-21%) inhibitory activity.