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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 Schramm   *
1   Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
,
Priyanka Saxena   *
2   Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
,
Jakub Chlebek
3   ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Hradec Králové, Czech Republic
,
Lucie Cahlíková
3   ADINACO Research Group, Department of Pharmaceutical Botany and Ecology, Charles University, Hradec Králové, Czech Republic
,
Igor Baburin
2   Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
,
Steffen Hering
2   Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria
,
Matthias Hamburger
1   Division of Pharmaceutical Biology, University of Basel, Basel, Switzerland
› Author Affiliations
Further Information

Publication History

received 27 February 2014
revised 02 May 2014

accepted 19 May 2014

Publication Date:
25 June 2014 (online)

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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.

Key words

natural products - hERG channel inhibition - Xenopus oocyte assay - plant-derived alkaloids - in vitro library screening

* These authors contributed equally to this work.


Supporting Information

 

  • References

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