Ciguatoxins and brevetoxins, neurotoxic polyether compounds active on sodium channels

Dechraoui, M. Yasmine Bottein; Naar, Jérôme; Pauillac, Serge; Legrand, Anne‐Marie

doi:10.1016/s0041-0101(98)00169-x

Cited by 227 publications

(165 citation statements)

References 32 publications

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“…5a, b). Like STX and TTX, they both act upon the Na channel (Dechraoui et al 1999(Dechraoui et al , 2006Gawley et al 1992;Lombet et al 1987), but at a different location within its structure. Rather than inhibit Na flow, their action shifts the voltage at which the Na channel responds to changes in potential difference across the cell membrane Sheridan and Adler 1989).…”

Section: Other Marine Toxins That Inhibit Sodium Channel Functionmentioning

confidence: 99%

“…Brevetoxins and ciguatoxins bind to sensitive channels at nanomolar or even lower concentrations (Dechraoui et al 1999;Poli et al 1986). Only recently have insensitive Na channel subtypes been discovered (Dechraoui et al 2006) with rat heart Na channels being significantly less sensitive to the brevetoxins and ciguatoxins.…”

Section: Other Marine Toxins That Inhibit Sodium Channel Functionmentioning

confidence: 99%

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Developmental Biology of Neoplastic Growth

Macieira‐Coelho¹

2005

Progress in Molecular and Subcellular Biology

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Section: Other Marine Toxins That Inhibit Sodium Channel Functionmentioning

confidence: 99%

Section: Other Marine Toxins That Inhibit Sodium Channel Functionmentioning

confidence: 99%

Developmental Biology of Neoplastic Growth

Macieira‐Coelho¹

2005

Progress in Molecular and Subcellular Biology

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“…Ciguatoxins and brevetoxins share a specific binding site on the voltage-sensitive sodium channels (19,20), although ciguatoxins bind 10 times more strongly than brevetoxins (21,22). The site specificity and selective function of these toxins may present an opportunity for investigation into the activation and gating mechanisms of the channel itself.…”

mentioning

confidence: 99%

First- and second-generation total synthesis of ciguatoxin CTX3C

Inoue

Miyazaki

Uehara

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

117

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More than 20,000 people suffer annually from ciguatera seafood poisoning in subtropical and tropical regions. The extremely low content of the causative neurotoxins, designated as ciguatoxins, in fish has hampered isolation, detailed biological studies, and preparation of anti-ciguatoxin antibodies for detecting these toxins. Furthermore, the large (3 nm in length) and complex molecular structure of ciguatoxins has impeded chemists from completing their total synthesis. In this article, the full details of studies leading to the total synthesis of ciguatoxin CTX3C are provided. The key elements of the first-generation approach include O,O-acetal formation from the right and left wing fragments, conversion from O,O-acetal to O,S-acetal, a radical reaction to cyclize the G ring, a ring-closing metathesis reaction to close the F ring, and final removal of the 2-naphtylmethyl protective groups. Subsequent studies provided a second-generation total synthesis, which is more concise and results in a higher yield. Second-generation synthesis was accomplished by using a direct method of constructing the key intermediate O,S-acetal from ␣-chlorosulfide and a secondary alcohol. These syntheses ensure a practical supply of ciguatoxin for biological applications.ciguatera ͉ polyether ͉ convergent strategy C iguatera is a human intoxication caused by the ingestion of certain reef fish (1). More than 20,000 people suffer annually from ciguatera, making it one of the most common forms of nonbacterial food poisoning. Ingestion of affected fish leads to neurological, gastrointestinal, and cardiovascular disorders, which may last up to a month or more. The most prominent symptom is a disorder of temperature sensation. Specifically, touching cold water can induce pain similar to that of an electric shock. Other symptoms include diarrhea, vomiting, muscle pain and itching, whereas paralysis, coma, and even death may occur in severe cases.Yasumoto et al. (2) identified an epiphytic dinoflagellate, Gambierdiscus toxicus, as the causative organism and demonstrated that dinoflagellate-derived toxins are transferred by the food chain to various fish. About 100 species of fish cause ciguatera, and ciguateric fish look, taste, and smell like normal uncontaminated fish. In addition, the occurrence of poisoning is completely unpredictable. Current difficulties in predicting, detecting, and treating ciguatera have had an adverse socioeconomic impact, in particular, in developing countries.Ciguatoxins are regarded as the principal causative toxins of ciguatera seafood poisoning (Fig. 1) (3, 4). In 1989, the Yasumoto group successfully elucidated the structures of ciguatoxin (CTX) (4) and CTX4B (3) (5, 6), which were found to be large polycyclic ethers having molecular lengths Ͼ3 nm. They subsequently isolated other congeners including CTX3C (1) (7) and 51-hydroxyCTX3C (2) (8). To date, the structures of Ͼ20 congeners of ciguatoxins have been determined (9, 10).The lethal potencies of ciguatoxins (LD 50 ϭ 0.25-4 g͞kg) by i.p. injection into mic...

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“…Bourdelais et al 2005) Not all types are naturally occurring; some, such as PbTx-8, a chloromethyl ketone derivative of PbTx-2, is an artifact of chloroform extraction of PbTx-2 (Nakanishi 1985;Baden 1989;Ishida et al 2004;Baden et al 2005;Twiner et al 2007;Murrell and Gibson 2009). As the typical neurotoxins, brevetoxins have the ability to bind to site 5 of the voltagegated sodium channels (Poli et al 1986;Trainer et al 1990;Manger et al 1995;Dechraoui et al 1999). Performing as depolarizers, brevetoxins can open the voltage-gated sodium channels located in cell walls, thus altering the properties of the membrane and assisting the inward flow of sodium ions into the cells, resulting in the persistent activation of the cell leading to the eventual paralysis of the enervated cells (Poli et al 1986;Trainer et al 1990;Manger et al 1995;Dechraoui et al 1999).…”

Section: Brevetoxinsmentioning

confidence: 99%

“…As the typical neurotoxins, brevetoxins have the ability to bind to site 5 of the voltagegated sodium channels (Poli et al 1986;Trainer et al 1990;Manger et al 1995;Dechraoui et al 1999). Performing as depolarizers, brevetoxins can open the voltage-gated sodium channels located in cell walls, thus altering the properties of the membrane and assisting the inward flow of sodium ions into the cells, resulting in the persistent activation of the cell leading to the eventual paralysis of the enervated cells (Poli et al 1986;Trainer et al 1990;Manger et al 1995;Dechraoui et al 1999). The consumption of brevetoxins contaminated seafood has the potential to disrupt normal neurological processes causing the illness clinically described as neurotoxic shellfish poisoning (NSP) (Truman et al 2002;Naar et al 2007;Twiner et al 2007).…”

Section: Brevetoxinsmentioning

confidence: 99%

Interactions of Toxic Metals with Algal Toxins Derived from Harmful Algal Blooms

Li¹

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The purposes of this study were to characterize the complexation of toxic metals with algal toxins and to determine the effects of arsenic and copper on the growth of Karenia brevis under specific experimental conditions. Microcystins, pahayokolides, brevetoxins and okadaic acid were used as representatives of algal toxins while arsenic, copper, cadmium, cobalt, iron, manganese and mercury were selected as typical toxic metals (including metalloids here) in the aquatic environment. The stabilities of the toxin-metal complexes were determined using equilibrium dialysis and/or centrifugal ultrafiltration technique. A direct exposure of arsenic and copper to the K. brevis was carried out to determine the effects of these metals to the growth of the algal cell.

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Ciguatoxins and brevetoxins, neurotoxic polyether compounds active on sodium channels

Cited by 227 publications

References 32 publications

Developmental Biology of Neoplastic Growth

Developmental Biology of Neoplastic Growth

First- and second-generation total synthesis of ciguatoxin CTX3C

Interactions of Toxic Metals with Algal Toxins Derived from Harmful Algal Blooms

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