Uracil moiety is required for toxicity of the cyanobacterial hepatotoxin cylindrospermopsin.
A new natural derivative of the sulfated guanidinium zwitterionic toxin cylindrospermopsin, 7-epi-cylindrospermopsin, was recently isolated from the cyanobacterium Aphanizomenon ovalisporum (Forti). The toxicity of the molecule (LD50 ip 5 d), estimated by mouse bioassay, was 200 microg/kg mouse, a value similar to that of cylindrospermopsin. Treatment of cylindrospermopsin with chlorine solution or chlorine-related oxidants produced two new derivatives. The chemical structure of these products was elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques and toxicity was determined. In the first derivative, the vinylic proton at position 5 of the pyrimidine ring was substituted by chlorine to yield 5-chlorocylindrospermopsin. The other product is a truncated one, where C-6 of the pyrimidine ring was oxidized to a carboxylic acid. A trivial name, cylindrospermic acid, was given to this compound. Both products showed no toxic effects even at doses 50 times higher than the LD50 of cylindrospermopsin (10 mg/kg mouse ip). Based on these results, the pyrimidine ring is postulated as the molecule component essential for the toxicity of cylindrospermopsin.
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv, Israel.
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R
Banker
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Carmeli
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M
Werman
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B
Teltsch
R
R
Porat
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A
Sukenik
D000470:Alkaloids; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry* / Q000633:toxicity*; D001681:Biological Assay; D002700:Chloramines / Q000737:chemistry; D017606:Chlorine Compounds / Q000737:chemistry; D000458:Cyanobacteria; D000087522:Cyanobacteria Toxins; D008099:Liver / Q000187:drug effects*; D008387:Marine Toxins / Q000737:chemistry* / Q000633:toxicity*; D051379:Mice; D052998:Microcystins; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000633:toxicity*
D000470:Alkaloids; D001427:Bacterial Toxins; D002700:Chloramines; D017606:Chlorine Compounds; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D010087:Oxides; C089595:cylindrospermopsin; D014498:Uracil; C025109:chlorine dioxide; C030816:chloramine