Diterpene Alkaloids from Aconitum anthora and Assessment of the hERG-Inhibiting Ability of Aconitum Alkaloids

Peter Forgo; Botond Borcsa; Dezső Csupor; László Fodor; Róbert Berkecz; Attila Molnár V.; Judit Hohmann

doi:10.1055/s-0030-1250362

Planta Medica, Table of Contents

Planta Med 2011; 77(4): 368-373
DOI: 10.1055/s-0030-1250362

Natural Product Chemistry

Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Diterpene Alkaloids from Aconitum anthora and Assessment of the hERG-Inhibiting Ability of Aconitum Alkaloids

Peter Forgo¹ , Botond Borcsa¹ , Dezső Csupor¹ , László Fodor² , Róbert Berkecz³ , Attila Molnár V.⁴ , Judit Hohmann¹

¹Department of Pharmacognosy, University of Szeged, Szeged, Hungary
²Gedeon Richter Plc., Budapest, Hungary
³Department of Medical Chemistry, University of Szeged, Szeged, Hungary
⁴Department of Botany, University of Debrecen, Debrecen, Hungary

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.

Key words

Aconitum anthora - Ranunculaceae - aconitine - diterpene alkaloids - hERG - potassium channels

Full Text

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Prof. Judit Hohmann

Department of Pharmacognosy
University of Szeged

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Hungary

Phone: +36 62 54 64 53

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Email: hohmann@pharm.u-szeged.hu