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Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers.

ABSTRACT: 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 ?M 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.

SUBMITTER: De Oliveira EO

PROVIDER: S-EPMC3134794 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Synthesis and evaluation of hermitamides A and B as human voltage-gated sodium channel blockers.

De Oliveira Eliseu O EO Graf Kristin M KM Patel Manoj K MK Baheti Aparna A Kong Hye-Sik HS MacArthur Linda H LH Dakshanamurthy Sivanesan S Wang Kan K Brown Milton L ML Paige Mikell M

Bioorganic & medicinal chemistry 20110530 14

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 ...[more]

PMID: 21683602

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