Planta Med 2014; 80(08/09): 740-746
DOI: 10.1055/s-0034-1368590
Biological Screening
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Natural Products as Potential Human Ether-A-Go-Go-Related Gene Channel Inhibitors – Screening of Plant-Derived Alkaloids

Anja Schramm1, *, Priyanka Saxena2, *, Jakub Chlebek3, Lucie Cahlíková3, Igor Baburin2, Steffen Hering2, Matthias Hamburger1
  • 1Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
  • 2Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
  • 3ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Hradec Králové, Czech Republic
Weitere Informationen

Publikationsverlauf

received 27. Februar 2014
revised 02. Mai 2014

accepted 19. Mai 2014

Publikationsdatum:
25.Juni 2014 (online)

Abstract

Inhibition of the cardiac human ether-a-go-go-related gene channel is a problematic off-target pharmacological activity and, hence, a major safety liability in clinical practice. Several non-cardiac drugs have been restricted in their use, or even removed from the market due to this potentially fatal adverse effect. Comparatively little is known about the human ether-a-go-go-related gene inhibitory potential of plant-derived compounds. In the course of an ongoing human ether-a-go-go-related gene in vitro study, a total of 32 structurally diverse alkaloids of plant origin as well as two semi-synthetically obtained protoberberine derivatives were screened by means of an automated Xenopus oocyte assay. Protopine, (+)-bulbocapnine, (+)-N-methyllaurotetanine, (+)-boldine, (+)-chelidonine, (+)-corynoline, reserpine, and yohimbine reduced the human ether-a-go-go-related gene current by ≥ 50 % at 100 µM, and were submitted to concentration-response experiments. Our data show that some widely occurring plant-derived alkaloids carry a potential risk for human ether-a-go-go-related gene toxicity.

* These authors contributed equally to this work.


Supporting Information