# Determination of Cyanotoxins and Prymnesins in Water, Fish Tissue, and Other Matrices: A Review
## 2 Cyanotoxins and Prymnesins  
Cyanotoxins can be categorized based on (1) their mechanism of action on terrestrial vertebrates, especially mammals, e.g., hepatotoxins, neurotoxins, and dermatotoxins, and (2) their chemical structure, e.g., cyclic peptides, alkaloids, and lipopolysaccharide [22; 23; 24]. Table 1 lists the names, chemical groups, and mammalian targets of some common cyanotoxins. Physicochemical properties of cyanotoxins not only determine which extraction procedures or detection techniques are suitable but also impact the bioaccumulative and toxicological properties of the toxins on several taxa of aquatic invertebrates and vertebrates [25]. MCs, the most studied class of cyanotoxin, are produced several cyanobacterial genera including _Microystis_, _Anabaena_, _Hapalosiphon_, _Nostoc_, _Dolichospermum_, _Gleootrichia_, and _Oscillatoria_[12]. These compounds are short cyclic heptapeptides synthesized by non-ribosomal pathways [26]. MCs are characterized by significant structural variability in amino acid composition, including residue substitutions, methylations, and demethylations. In total, more than 248 congeners/variants have been reported in the environment. Among them, MC-LR and MC-LA are among the most toxic [27; 28]. Only a limited subset of MCs has commercially available analytical standards, which limits the scope of quantitative methods, such as LC-MS/MS, which rely on these for accurate quantification. MCs are cytotoxic and inhibit protein phosphatases, which leads to several subsequent harmful effects at concentrations over 10 \(\mathrm{\SIUnitSymbolMicro g}\)/L [29]. Nodularins (NODs) are a class of cyclic pentapeptides structurally similar to MCs. Currently, 10 variants of this water-soluble and stable toxin have been identified [30; 31], the most common being the variant with arginine as the variable amino acid (NOD-R). Similar to MCs, NODs are hepatotoxins acting through the inhibition of protein phosphatases and are potential tumor promoters. While NODs have historically been considered to be less common than MCs, their occurrence has been observed in bloom events corresponding to the species _Nodularia spunigena_, and animal deaths have been reported [31]. Anatoxin-a (ANA-a) and its structural variants have been associated with the genus _Anabena_ (now _Anabaena_/_Dolichospermum_) and also to _Aphanizomenon_; _Planktonrix_; _Cylindrospermum_; _Micocystis_; and the benthic _Oscillatoria_, _Phormidium_, _Tychonema_, and _Geitler-inema_[32]. ANA-a is an alkaloid known to exhibit acetylcholinesterasecholinesteraseerase inhibition activity, which is its primary mode of toxicity. Of the structural variants of ANA-a, homoanatoxin-a, resulting from the methylation of the carbon at the extremity of the ketone function, is one of the more commonly observed [33]. Several other derivatives of ANA-a have been identified, including 2,3-epoxy-anatoxin-a; 4-hydroxy- and 4-oxo-derivatives; dihydroanatoxin-a; and dihydroonanatoxin-a [34; 35]. Toxicity indications for these other variants are mixed, with some reports indicating lower toxicity while others suggesting higher oral toxicity from the dihydroanatoxin variant specifically, suggesting that monitoring of these variants is of interest [36]. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Common Name** & **Chemical Group** & **Effect/Target in Mammals** \\ \hline Microcystins & Heptapeptide & Cytotoxicity; genotoxic effects in liver \\ \hline Nodularins & Pentapeptide & Cytotoxicity; liver \\ \hline Anatoxin-a & Bicyclic amine alkaloid & Neurotoxicity \\ \hline Savitoxins & Tricyclic perhydropurine alkaloids & Neurotoxicity \\ \hline \(\beta\)-N-methylamino-L-alanine & Amino acid & Neurotoxicity \\ \hline Cylindrospermopsins & Polycyclic uracil with guanidine and sulfate group & Multitarget alkaloids \\ \hline Prymnesins & Polyether polycyclic core with several conjugate double and triple bonds & Hemolytic activity and ichthyotoxicity \\ \hline \hline \end{tabular}
\end{table}