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Planta Med 2014; 80(02/03): 231-236
DOI: 10.1055/s-0033-1360278
Natural Product Chemistry
Letters
Georg Thieme Verlag KG Stuttgart · New York

Diterpene Alkaloids from the Roots of Aconitum moldavicum and Assessment of Nav 1.2 Sodium Channel Activity of Aconitum Alkaloids

Botond Borcsa
1   Department of Pharmacognosy, University of Szeged, Szeged, Hungary
,
László Fodor
2   Gedeon Richter Plc., Budapest, Hungary
,
Dezső Csupor
1   Department of Pharmacognosy, University of Szeged, Szeged, Hungary
,
Peter Forgo
1   Department of Pharmacognosy, University of Szeged, Szeged, Hungary
,
Attila Molnár V.
3   Department of Botany, University of Debrecen, Debrecen, Hungary
,
Judit Hohmann
1   Department of Pharmacognosy, University of Szeged, Szeged, Hungary
› Author Affiliations
Further Information

Publication History

received 17 May 2013
revised 07 October 2013

accepted 16 December 2013

Publication Date:
22 January 2014 (online)

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Abstract

A new aconitane alkaloid, 1-O-demethylswatinine (1), was isolated from the root of Aconitum moldavicum together with the known compounds cammaconine (2), columbianine (3), swatinine (4), gigactonine (5), delcosine (6), lycoctonine (7), and ajacine (8). The structures were established by means of HRESIMS, 1D and 2D NMR spectroscopy, including 1H-1H COSY, NOESY, HSQC, and HMBC experiments, resulting in complete 1H-NMR chemical shift assignments for 1–4. The effects of the isolated compounds 4–8, together with eighteen other Aconitum diterpene and norditerpene alkaloids with different skeletal types and substitution patterns, were studied on Nav 1.2 channels by the whole-cell patch clamp technique, using the QPatch-16 automated patch clamp system. Pyroaconitine, ajacine, septentriodine, and delectinine demonstrated significant Nav 1.2 channel inhibition (57–42 %) at 10 µM concentration; several other compounds (acovulparine, acotoxicine, hetisinone, 14-benzoylaconine-8-O-palmitate, aconitine, and lycoctonine) exerted moderate inhibitory activity (30–22 %), while the rest of the tested alkaloids were considered to be inactive. On the basis of these results and by exhaustive comparison of data of previously published computerized QSAR studies on diterpene alkaloids, certain conclusions on the structure-activity relationships of Aconitum alkaloids concerning Nav 1.2 channel inhibitory activity are proposed.

Key words

Aconitum moldavicum - Ranunculaceae - aconitine - norditerpene alkaloids - Nav 1.2 sodium channel inhibitory activity

Supporting Information

 

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