Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers
| Autor: | Manoj K. Patel, Eliseu O. De Oliveira, Aparna Baheti, K. Graf, Linda MacArthur, Sivanesan Dakshanamurthy, Milton L. Brown, Kan Wang, Hye-Sik Kong, Mikell Paige |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Indoles Stereochemistry Clinical Biochemistry Molecular Conformation Pharmaceutical Science Stereoisomerism Biochemistry Sodium Channels Article Cell Line Structure-Activity Relationship Sodium channel blocker Drug Discovery Phenethylamines Structure–activity relationship Humans Voltage-Gated Sodium Channel Blockers Molecular Biology Lyngbya majuscula biology Chemistry Sodium channel Organic Chemistry Total synthesis biology.organism_classification Amides Electrophysiology Molecular Medicine Sodium Channel Blockers |
| Zdroj: | Bioorganicmedicinal chemistry. 19(14) |
| ISSN: | 1464-3391 |
| Popis: | Hermitamides A and B are lipopeptides isolated from a Papau New Guinea collection of the marine cyanobacterium Lyngbya majuscula. We hypothesized that the hermitamides are ligands for the human voltage-gated sodium channel (hNa(V)) based on their structural similarity to the jamaicamides. Herein, we describe the nonracemic total synthesis of hermitamides A and B and their epimers. We report the ability of the hermitamides to displace [(3)H]-BTX at 10 μM more potently than phenytoin, a clinically used sodium channel blocker. We also present a potential binding mode for (S)-hermitamide B in the BTX-binding site and electrophysiology showing that these compounds are potent blockers of the hNav1.2 voltage-gated sodium channel. |
| Databáze: | OpenAIRE |
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