Diterpene alkaloids from Aconitum anthora and assessment of the hERG-inhibiting ability of Aconitum alkaloids.
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.
Forgo
Peter
P
Department of Pharmacognosy, University of Szeged, Szeged, Hungary.
Borcsa
Botond
B
Csupor
Dezso
D
Fodor
László
L
Berkecz
Róbert
R
Molnár V
Attila
A
Hohmann
Judit
J
D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots; D026902:Potassium Channel Blockers / Q000302:isolation & purification / Q000494:pharmacology*
C562101:10-hydroxy-8- O-methyltalatizamine; D000470:Alkaloids; D004224:Diterpenes; D051638:Ether-A-Go-Go Potassium Channels; D010936:Plant Extracts; D026902:Potassium Channel Blockers