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 - Na
v 1.2 sodium channel inhibitory activity
