Ciguatoxins

Ciguatoxins (CTX) are a group of about twenty built complex, structurally closely related, high neurotoxic polycyclic poly ethers . They are metabolic products of marine dinoflagellates and contribute to ciguatera , food poisoning. The Ciguatoxin is synonymous with Ciguatoxin CTX1B.

history

The structure of the ciguatoxin CTX1B was elucidated in 1989. For this purpose, only 0.36 mg of the toxin were isolated from 4150 kg of giant moray eels ( Gymnothorax javanicus ). This small amount was nevertheless sufficient to elucidate the very complex structure of this polyether. In the last steps to purify the toxin by means of column chromatography , mice were injected with the eluate for fraction detection. When the mouse died, the toxin was in the respective fraction.

A first total synthesis of a ciguatoxin (CTX3C), the complex structure of which contains 13 rings of cyclic ethers with 30 stereocenters, was published in 2001.

Occurrence

They are metabolic products of the dinoflagellates Gambierdiscus toxicus, which are widespread in subtropical and tropical regions of the Pacific Ocean , the Indian Ocean and the Caribbean . These toxins accumulate in the marine food chains , as a result of which human fish can also contain effective doses of the ciguatoxins.

Interestingly, the actual ciguatoxin CTX1B is not found as a direct metabolic product of the dinoflagellate, but only appears in higher trophic levels . The representatives of these levels also tend to contain more highly hydroxylated derivatives, while more non-polar representatives can be isolated from cultures of the Gambier discus toxicus (e.g. CTX3C). This fact is due to the metabolism of the ciguatoxins in the animal organism. Since the toxicity increases sharply with the increasingly hydrophilic character of the compound, in addition to the accumulation of the toxins, their effect potentiation also occurs in the food chain. CTX1B is about ten times more toxic than CTX4B, which has three hydroxyl groups.

properties

Ciguatoxins are colorless oils. They are relatively resistant to chemicals. For example, they are not destroyed by cooking when preparing food.

Biological importance

Eating fish contaminated with ciguatoxin causes severe, but rarely fatal, food poisoning , known as ciguatera . Ciguatoxins bind to voltage-activated sodium channels and cause their permanent activation. Typical signs of poisoning are numbness in the extremities, paresthesias , disturbances in the feeling of warm and cold and vomiting. The symptoms can last for days, but often weeks or even years. The poisoning can only be treated symptomatically as no antidote is available.

The LD ₅₀ on intraperitoneal intake for mice is 1.64 µg / kg for CTX1B and 6.24 µg / kg for CTX3C.

Representative

Surname	CAS	PubChem	Sum formula	Remarks
CTX1B Ciguatoxin	11050-21-8	5311333	C ₆₀ H ₈₆ O ₁₉
CTX2 52-epi-ciguatoxin 3	142185-85-1	6441260	C ₆₀ H ₈₆ O ₁₈	Diastereomer of Ciguatoxin-3, differs only in the absolute configuration of the C-52 atom
CTX3	139341-09-6	6444399	C ₆₀ H ₈₆ O ₁₈	Diastereomer of Ciguatoxin-2, differs only in the absolute configuration of the C-52 atom
CTX3C	148471-85-6	6442245	C ₅₇ H ₈₂ O ₁₆	CTX3C is one of the less polar compounds of the ciguatoxins and therefore has a lower toxic effect
51-hydroxy-CTX3C			C ₅₇ H ₈₂ O ₁₇
CTX4A			C ₆₀ H ₈₄ O ₁₆	Diastereomer of CTX4B
CTX4B Scaritoxin Gambier toxin 4b 52-epi-ciguatoxin 4A	123676-76-6 66231-73-0	6450530	C ₆₀ H ₈₄ O ₁₆	Diastereomer of CTX4A
CTX4C	136252-00-1

Web links

Individual evidence

↑ AM Legrand, M. Litaudon, JN Genthon, R. Bagnis, T. Yasumoto: Isolation and some properties of ciguatoxin . In: Journal of Applied Phycology . tape 1 , no. 2 , August 1989, p. 183-188 , doi : 10.1007 / bf00003882 .
↑ M. Murata, AM Legrand, Y. Ishibashi, T. Yasumoto: Structures and configurations of ciguatoxin from the moray eel Gymnothorax javanicus and its likely precursor from the dinoflagellate Gambierdiscus toxicus . In: J. Am. Chem. Soc. 111: 8929 (1989).
↑ M. Hirama, T. Oishi, H. Uehara, M. Inoue, M. Maruyama, H. Oguri, M. Satake: Total synthesis of ciguatoxin CTX3C. In: Science . 294, 1904 (2001).
↑ T. Anger, DJ Madge, M. Mulla, D. Riddall: Medicinal chemistry of neuronal voltage-gated sodium channel blockers. In: J. Med. Chem. 44, 115 (2001).
↑ Hiroki Oguri: Bioorganic Studies Utilizing Rationally Designed Synthetic Molecules: Absolute Configuration of Ciguatoxin and Development of Immunoassay Systems. In: Bulletin of the Chemical Society of Japan. 80, 2007, p. 1870, doi: 10.1246 / bcsj.80.1870 .
↑ Luis M. Botana; Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection ; ISBN 978-0-8247-8956-5 .

[1] AM Legrand, M. Litaudon, JN Genthon, R. Bagnis, T. Yasumoto: Isolation and some properties of ciguatoxin . In: Journal of Applied Phycology . tape 1 , no. 2 , August 1989, p. 183-188 , doi : 10.1007 / bf00003882 .

[2] M. Murata, AM Legrand, Y. Ishibashi, T. Yasumoto: Structures and configurations of ciguatoxin from the moray eel Gymnothorax javanicus and its likely precursor from the dinoflagellate Gambierdiscus toxicus . In: J. Am. Chem. Soc. 111: 8929 (1989).

[3] M. Hirama, T. Oishi, H. Uehara, M. Inoue, M. Maruyama, H. Oguri, M. Satake: Total synthesis of ciguatoxin CTX3C. In: Science . 294, 1904 (2001).

[4] T. Anger, DJ Madge, M. Mulla, D. Riddall: Medicinal chemistry of neuronal voltage-gated sodium channel blockers. In: J. Med. Chem. 44, 115 (2001).

[5] Hiroki Oguri: Bioorganic Studies Utilizing Rationally Designed Synthetic Molecules: Absolute Configuration of Ciguatoxin and Development of Immunoassay Systems. In: Bulletin of the Chemical Society of Japan. 80, 2007, p. 1870, doi: 10.1246 / bcsj.80.1870 .

[6] Luis M. Botana; Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection ; ISBN 978-0-8247-8956-5 .