TY - JOUR
T1 - Hoiamide A, a Sodium Channel Activator of Unusual Architecture from a Consortium of Two Papua New Guinea Cyanobacteria
AU - Pereira, Alban
AU - Cao, Zhengyu
AU - Murray, Thomas F.
AU - Gerwick, William H.
N1 - Funding Information:
We thank D. Edwards and L. T. Simmons for collection of the assemblage of L. majuscula and P. gracile from Papua New Guinea, as well as A. Jansma and X. Huang for assistance with the Bruker 600 MHz TCI cryoprobe and Bruker 800 MHz NMR spectrometers, respectively. We appreciate N. Engene's input in the morphological characterization and taxonomic identification of the source organisms. Support of chemical and pharmacological aspects of the work was provided by NIH (NS053398).
PY - 2009/8/28
Y1 - 2009/8/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.chembiol.2009.06.012
DO - 10.1016/j.chembiol.2009.06.012
M3 - Article
C2 - 19716479
AN - SCOPUS:69049091880
VL - 16
SP - 893
EP - 906
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 8
ER -