Abstract |
Contribution of the C-8 hydroxyl group of tetrodotoxin to its sodium channel blocking activity has never been clearly evaluated. Isobe et al. recently synthesized 8,11-dideoxytetrodotoxin, the first 8-deoxy analog of tetrodotoxin. In this study, the biological activity of this compound was investigated to compare with that of 11-deoxytetrodotoxin. Intraperitoneal injection of 8,11-dideoxytetrodotoxin at the level of 700 microg/kg did not kill a mouse (n=2), indicating that the lethal dose of this compound was more than 70 and 10 folds larger than LD(50) of tetrodotoxin and 11-deoxytetrodotoxin, respectively. The inhibitory activity of 8,11-dideoxytetrodotoxin to cytotoxicity of ouabain and veratridine in mouse neuroblastoma cells (Neuro-2a) was also examined. The ED(50) for 8,11-dideoxytetrodotoxin was estimated to be 9.3+/-3.3 microM (n=3), approximately 2000 and 34 folds larger than those of tetrodotoxin (4.6+/-0.70 nM, n=3) and 11-deoxytetrodotoxin (270+/-74 nM, n=4), respectively. These data suggest that the C-8 hydroxyl group of tetrodotoxin is also important for its activity, as well as all the other hydroxyl groups.
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Authors | Mari Yotsu-Yamashita, Daisuke Urabe, Masanori Asai, Toshio Nishikawa, Minoru Isobe |
Journal | Toxicon : official journal of the International Society on Toxinology
(Toxicon)
Vol. 42
Issue 5
Pg. 557-60
(Oct 2003)
ISSN: 0041-0101 [Print] England |
PMID | 14529738
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 8,11-dideoxytetrodotoxin
- Enzyme Inhibitors
- 11-deoxytetrodotoxin
- Tetrodotoxin
- Ouabain
- Veratridine
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Topics |
- Animals
- Cell Line, Tumor
- Cell Survival
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(toxicity)
- Injections, Intraperitoneal
- Lethal Dose 50
- Male
- Mice
- Mice, Inbred Strains
- Neuroblastoma
(metabolism)
- Ouabain
(toxicity)
- Structure-Activity Relationship
- Tetrodotoxin
(analogs & derivatives, toxicity)
- Veratridine
(toxicity)
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