Hoiamide a, a sodium channel activator of unusual architecture from a consortium of two papua new Guinea cyanobacteria.
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 alpha-methylated thiazolines and one thiazole, and a highly oxygenated and methylated C15-polyketide substructure. Pure hoiamide A potently inhibited [(3)H]batrachotoxin binding to voltage-gated sodium channels (IC(50) = 92.8 nM), activated sodium influx (EC(50) = 2.31 microM) 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.
Pereira
Alban
A
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, 92093, USA.
Cao
Zhengyu
Z
Murray
Thomas F
TF
Gerwick
William H
WH
D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D001665:Binding Sites; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010219:Papua New Guinea; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D062687:Sodium Channel Agonists; D015222:Sodium Channels / Q000378:metabolism; D013237:Stereoisomerism
D001496:Batrachotoxins; D047630:Depsipeptides; D016194:Receptors, N-Methyl-D-Aspartate; D062687:Sodium Channel Agonists; D015222:Sodium Channels; C545734:hoiamide A; D012964:Sodium