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Fitoterapia ; 94: 120-6, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24508249

ABSTRACT

Two new diterpenoid alkaloids, Guan-Fu base J (GFJ, 1) and Guan-Fu base N (GFN, 2) along with nineteen known alkaloids (3-21) were isolated from the roots of Aconitum coreanum (Lèvl.) Rapaics, which is the raw material of a new approval anti-arrhythmia drug "Acehytisine Hydrochloride". The structures of isolated compounds were established by means of 1D, 2D NMR spectroscopic and chemical methods. All isolates obtained in the present study were evaluated for their inhibitory effects on blocking the ventricular specific sodium current using a whole-cell patch voltage-clamp technique. Among these 21 compounds, Guan-Fu base S (GFS, 3) showed the strongest inhibitory effect with an IC50 value of 3.48 µM, and only hetisine-type C20 diterpenoid alkaloids showed promising IC50 values for further development.


Subject(s)
Aconitum/chemistry , Alkaloids/chemistry , Anti-Arrhythmia Agents/chemistry , Diterpenes/chemistry , Plant Extracts/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Anti-Arrhythmia Agents/isolation & purification , Anti-Arrhythmia Agents/pharmacology , Diterpenes/isolation & purification , Diterpenes/pharmacology , Dose-Response Relationship, Drug , Guinea Pigs , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Male , Membrane Potentials/drug effects , Molecular Structure , Myocytes, Cardiac/drug effects , Patch-Clamp Techniques , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Roots/chemistry , Sodium/physiology
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