Guanitoxin

Last updated
Guanitoxin
Anatoxin-a(S) skeletal.svg
Names
IUPAC name
(5S)-5-[(Dimethylamino)methyl]-1-{[hydroxy(methoxy)phosphoryl]oxy}-4,5-dihydro-1H-imidazol-2-amine
Identifiers
3D model (JSmol)
ChemSpider
KEGG
PubChem CID
UNII
  • InChI=1S/C7H17N4O4P/c1-10(2)5-6-4-9-7(8)11(6)15-16(12,13)14-3/h6H,4-5H2,1-3H3,(H2,8,9)(H,12,13)/t6-/m1/s1
    Key: FYXHGVMFJYHPFX-ZCFIWIBFSA-N
  • CN(C)C[C@H]1CN=C(N1OP(=O)(O)OC)N
Properties
C7H17N4O4P
Molar mass 252.211 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Guanitoxin (GNT), formerly known as anatoxin-a(S) "Salivary" [a] , [1] is a naturally occurring cyanotoxin commonly isolated from cyanobacteria (specifically of the genus Anabaena). It is a potent covalent acetylcholinesterase inhibitor, and thus a potent rapid acting neurotoxin which in cases of severe exposure can lead to death. Guanitoxin was first structurally characterized in 1989, and consists of a cyclic N-hydroxyguanidine organophosphate with a phosphate ester moiety. [2]

Contents

Toxicity and treatment

The main mechanism of action for guanitoxin is by irreversibly inhibiting the active site of acetylcholinesterase leading to excess acetylcholine in the parasympathetic and peripheral nervous systems; inducing poisoning via nicotinic and muscarinic cholinergic receptor stimulation. [3] The clinical signs of high level guanitoxin exposure consists mainly of excessive salivation, lacrimation, chromodacryorrhea (in rats), urinary incontinence, muscular weakness, muscle twitching, convulsion, including opisthotonus, and respiratory distress and/or failure, and death. [4] [5]

Treatment of afflicted case by atropine has attested to suppress the muscarinic mediated toxicity; which prevents the namesake salivation that similarly reacts to prevent the toxin's other poisoning symptoms which include lacrimation, urinary incontinence and defecation. Atropine will not, however, counter another mechanism of the compounds toxicity as it also mediates a nicotinic adverse toxicity affecting muscle tremors, fasciculation, convulsions and respiratory failure.[ citation needed ]

Stability and degradation

Guanitoxin is generally labile. It decomposes rapidly in basic solutions, but is relatively stable in neutral or acidic solutions (pH 3-5). When stored at -20˚C, it slowly undergoes hydrolysis giving pre-guanitoxin N-oxide and monomethyl-phosphate, and more slowly, formation of pre-guanitoxin. Furthermore, air evaporation of guanitoxin solutions resulted in significant hydrolysis to pre-guanitoxin N-oxide. [2]

Scheme for guanitoxin degradation. Major microspecies at pH 7.4 are shown. Scheme for Guanitoxin degradation.svg
Scheme for guanitoxin degradation. Major microspecies at pH 7.4 are shown.

See also

Footnotes

  1. ↑ (The "(S)" its name stands for 'salivary' indicating its manner of affliction to distinguish it from a toxin having otherwise the same conventional name. cf. "See also" for aforementioned compound of shared nomenclature.)

References

  1. ↑ Fiore, Marli Fátima; de Lima, Stella Thomaz; Carmichael, Wayne W.; McKinnie, Shaun M.K.; Chekan, Jonathan R.; Moore, Bradley S. (2020). "Guanitoxin, re-naming a cyanobacterial organophosphate toxin". Harmful Algae. 92 101737. Elsevier BV. Bibcode:2020HAlga..9201737F. doi:10.1016/j.hal.2019.101737. ISSN   1568-9883. PMID   32113603. S2CID   211725815.
  2. 1 2 Matsunaga, Shigeki; Moore, Richard E.; Niemczura, Walter P.; Carmichael, Wayne W. (1989). "Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae". Journal of the American Chemical Society. 111 (20). American Chemical Society (ACS): 8021–8023. Bibcode:1989JAChS.111.8021M. doi:10.1021/ja00202a057. ISSN   0002-7863.
  3. ↑ Hyde, E. G.; Carmichael, W. W. (1991). "Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7)". Journal of Biochemical Toxicology. 6 (3): 195–201. doi:10.1002/jbt.2570060305. PMID   1770503.
  4. ↑ Mahmood, Nik A.; Carmichael, Wayne W. (1986). "The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17". Toxicon. 24 (5). Elsevier BV: 425–434. Bibcode:1986Txcn...24..425M. doi:10.1016/0041-0101(86)90074-7. ISSN   0041-0101. PMID   3087030.
  5. ↑ Fernandes, Kelly; Ferraz, Humberto; Vereau, Fanny; Pinto, Ernani (2020-11-19). "Availability of Guanitoxin in Water Samples Containing Sphaerospermopsis torques-reginae Cells Submitted to Dissolution Tests". Pharmaceuticals. 13 (11). MDPI AG: 402. doi: 10.3390/ph13110402 . ISSN   1424-8247. PMC   7699232 . PMID   33227987.
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