Natural products as potential human ether-a-go-go-related gene channel inhibitors - screening of plant-derived alkaloids.
Planta Med
; 80(8-9): 740-6, 2014 Jun.
Article
em En
| MEDLINE
| ID: mdl-24963621
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Alcaloides de Berberina
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Produtos Biológicos
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Bloqueadores dos Canais de Potássio
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Alcaloides
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Canais de Potássio Éter-A-Go-Go
Tipo de estudo:
Diagnostic_studies
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Screening_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article