Myrsinane, Premyrsinane, and Cyclomyrsinane Diterpenes from Euphorbia falcata as Potassium Ion Channel Inhibitors with Selective G Protein-Activated Inwardly Rectifying Ion Channel (GIRK) Blocking Effects
| Autor: | Péter Orvos, Attila Csorba, Peter Forgo, Judit Hohmann, Andrea Vasas, Gyula Pinke, László Tálosi |
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| Rok vydání: | 2016 |
| Předmět: |
G protein
hERG Pharmaceutical Science Pharmacology 01 natural sciences Membrane Potentials Receptors G-Protein-Coupled Analytical Chemistry Euphorbia Drug Discovery Potassium Channel Blockers Animals G protein-coupled inwardly-rectifying potassium channel Receptor Ion channel Neurons Molecular Structure Atrium (architecture) biology urogenital system 010405 organic chemistry Chemistry Organic Chemistry Heart Transfection Potassium channel 0104 chemical sciences 010404 medicinal & biomolecular chemistry G Protein-Coupled Inwardly-Rectifying Potassium Channels Complementary and alternative medicine biology.protein Molecular Medicine Diterpenes |
| Zdroj: | Journal of Natural Products. 79:1990-2004 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | GIRK channels are activated by a large number of G protein-coupled receptors and regulate the electrical activity of neurons, cardiac atrial myocytes, and β-pancreatic cells. Abnormalities in GIRK channel function have been implicated in the pathophysiology of neuropathic pain, drug addiction, and cardiac arrhythmias. In the heart, GIRK channels are selectively expressed in the atrium, and their activation inhibits pacemaker activity, thereby slowing the heart rate. In the present study, 19 new diterpenes, falcatins A-S (1-19), and the known euphorprolitherin D (20) were isolated from Euphorbia falcata. The compounds were assayed on stable transfected HEK-hERG (Kv11.1) and HEK-GIRK1/4 (Kir3.1 and Kir3.4) cells. Blocking activity on GIRK channels was exerted by 13 compounds (61-83% at 10 μM), and, among them, five possessed low potency on the hERG channel (4-20% at 10 μM). These selective activities suggest that myrsinane-related diterpenes are potential lead compounds for the treatment of atrial fibrillation. |
| Databáze: | OpenAIRE |
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