Candelalides A-C: novel diterpenoid pyrones from fermentations of Sesquicillium candelabrum as blockers of the voltage-gated potassium channel Kv1.3.
[figure: see text] Blockers of the voltage-gated potassium channel Kv1.3 are potential immunosuppressants. Candelalides A-C are three novel diterpenoid pyrones that block this channel. The structure, stereochemistry, and activity against Kv1.3 are described.
Singh
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Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. sheo_singh@merck.com
Zink
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Dombrowski
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Dezeny
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Bills
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Felix
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Slaughter
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Goetz
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D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005285:Fermentation; D006999:Hypocreales / Q000254:growth & development; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051662:Kv1.1 Potassium Channel; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D004224:Diterpenes; D007166:Immunosuppressive Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011753:Pyrones; D011994:Recombinant Proteins; C431986:candelalide A; C431985:candelalide B; C431984:candelalide C; D051662:Kv1.1 Potassium Channel