Abstract
Primary fractions from the extract of a tropical red alga mixed with filamentous cyanobacteria, collected from Papua New Guinea, were active in a neurotoxicity assay. Bioassay-guided isolation led to two natural products (1,2) with relatively potent calcium ion influx properties. The more prevalent of the neurotoxic compounds (1) was characterized by extensive NMR, mass spectrometry, and X-ray crystallography, and shown to be identical to a polybrominated diphenyl ether metabolite present in the literature, but reported with different NMR properties. To clarify this anomalous result, we synthesized a candidate isomeric polybrominated diphenyl ether (3), but this clearly had different NMR shifts than the reported compound. We conclude that the original isolate of 3,4,5-tribromo-2-(2,4-dibromophenoxy)phenol was contaminated with a minor compound, giving rise to the observed anomalous NMR shifts. The second and less abundant natural product (2) isolated in this study was a more highly brominated species. All three compounds showed a low micromolar ability to increase intracellular calcium ion concentrations in mouse neocortical neurons as well as toxicity to zebrafish. Because polybrominated diphenyl ethers have both natural as well as anthropomorphic origins, and accumulate in marine organisms at higher trophic level (mammals, fish, birds), these neurotoxic properties are of environmental significance and concern.
| Original language | English |
|---|---|
| Pages (from-to) | 204-210 |
| Number of pages | 7 |
| Journal | Toxicon |
| Volume | 55 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Feb 2010 |
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All Science Journal Classification (ASJC) codes
- Toxicology
Cite this
Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium : Structure clarification and biological properties. / Suyama, Takashi L.; Cao, Zhengyu; Murray, Thomas F.; Gerwick, William H.
In: Toxicon, Vol. 55, No. 2-3, 02.2010, p. 204-210.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ichthyotoxic brominated diphenyl ethers from a mixed assemblage of a red alga and cyanobacterium
T2 - Structure clarification and biological properties
AU - Suyama, Takashi L.
AU - Cao, Zhengyu
AU - Murray, Thomas F.
AU - Gerwick, William H.
PY - 2010/2
Y1 - 2010/2
N2 - Primary fractions from the extract of a tropical red alga mixed with filamentous cyanobacteria, collected from Papua New Guinea, were active in a neurotoxicity assay. Bioassay-guided isolation led to two natural products (1,2) with relatively potent calcium ion influx properties. The more prevalent of the neurotoxic compounds (1) was characterized by extensive NMR, mass spectrometry, and X-ray crystallography, and shown to be identical to a polybrominated diphenyl ether metabolite present in the literature, but reported with different NMR properties. To clarify this anomalous result, we synthesized a candidate isomeric polybrominated diphenyl ether (3), but this clearly had different NMR shifts than the reported compound. We conclude that the original isolate of 3,4,5-tribromo-2-(2,4-dibromophenoxy)phenol was contaminated with a minor compound, giving rise to the observed anomalous NMR shifts. The second and less abundant natural product (2) isolated in this study was a more highly brominated species. All three compounds showed a low micromolar ability to increase intracellular calcium ion concentrations in mouse neocortical neurons as well as toxicity to zebrafish. Because polybrominated diphenyl ethers have both natural as well as anthropomorphic origins, and accumulate in marine organisms at higher trophic level (mammals, fish, birds), these neurotoxic properties are of environmental significance and concern.
AB - Primary fractions from the extract of a tropical red alga mixed with filamentous cyanobacteria, collected from Papua New Guinea, were active in a neurotoxicity assay. Bioassay-guided isolation led to two natural products (1,2) with relatively potent calcium ion influx properties. The more prevalent of the neurotoxic compounds (1) was characterized by extensive NMR, mass spectrometry, and X-ray crystallography, and shown to be identical to a polybrominated diphenyl ether metabolite present in the literature, but reported with different NMR properties. To clarify this anomalous result, we synthesized a candidate isomeric polybrominated diphenyl ether (3), but this clearly had different NMR shifts than the reported compound. We conclude that the original isolate of 3,4,5-tribromo-2-(2,4-dibromophenoxy)phenol was contaminated with a minor compound, giving rise to the observed anomalous NMR shifts. The second and less abundant natural product (2) isolated in this study was a more highly brominated species. All three compounds showed a low micromolar ability to increase intracellular calcium ion concentrations in mouse neocortical neurons as well as toxicity to zebrafish. Because polybrominated diphenyl ethers have both natural as well as anthropomorphic origins, and accumulate in marine organisms at higher trophic level (mammals, fish, birds), these neurotoxic properties are of environmental significance and concern.
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UR - http://www.scopus.com/inward/citedby.url?scp=72749113983&partnerID=8YFLogxK
U2 - 10.1016/j.toxicon.2009.07.020
DO - 10.1016/j.toxicon.2009.07.020
M3 - Article
C2 - 19638282
AN - SCOPUS:72749113983
VL - 55
SP - 204
EP - 210
JO - Toxicon
JF - Toxicon
SN - 0041-0101
IS - 2-3
ER -