Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria

Alban Pereira, Zhengyu Cao, Thomas F. Murray, William H. Gerwick

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Hoiamide A, a novel bioactive cyclic depsipeptide, was isolated from an environmental assemblage of the marine cyanobacteria Lyngbya majuscula and Phormidium gracile collected in Papua New Guinea. This stereochemically complex metabolite possesses a highly unusual structure, which likely derives from a mixed peptide-polyketide biogenetic origin, and includes a peptidic section featuring an acetate extended and S-adenosyl methionine modified isoleucine moiety, a triheterocyclic fragment bearing two α-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [3H]batrachotoxin binding to voltage-gated sodium channels (IC50 = 92.8 nM), activated sodium influx (EC50 = 2.31 μM) in mouse neocortical neurons, and exhibited modest cytotoxicity to cancer cells. Further investigation revealed that hoiamide A is a partial agonist of site 2 on the voltage-gated sodium channel.

Original languageEnglish
Pages (from-to)893-906
Number of pages14
JournalChemistry and Biology
Volume16
Issue number8
DOIs
StatePublished - Aug 28 2009

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Sodium Channel Agonists
Papua New Guinea
Cyanobacteria
Voltage-Gated Sodium Channels
Polyketides
Batrachotoxins
Bearings (structural)
Depsipeptides
Thiazoles
Isoleucine
Cytotoxicity
Metabolites
Methionine
Inhibitory Concentration 50
Neurons
Acetates
Sodium
Cells
Peptides
hoiamide A

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Molecular Biology
  • Clinical Biochemistry
  • Molecular Medicine
  • Pharmacology

Cite this

Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria. / Pereira, Alban; Cao, Zhengyu; Murray, Thomas F.; Gerwick, William H.

In: Chemistry and Biology, Vol. 16, No. 8, 28.08.2009, p. 893-906.

Research output: Contribution to journalArticle

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