Alkaloids saxitoxin

Wiese M, D Agostino PM, Mihali TK, Moffitt MC, Neilan BA (2010) Neurotoxic alkaloids saxitoxin and its analogs. Mar Drugs 8 2185-2211. doi 10.3390/md8072185... 

In a narrow sense, purine alkaloids comprise methylxanthines and methyluric acids [1]. This chapter, however, also includes information on cytokinins, which are purine ring-containing phytohormones, and the purine-like neurotoxin alkaloids, saxitoxin and tetrodotoxin. 

Na, K channels Aconitine and related diterpene alkaloids veratridine, zygadenine, and related steroidal alkaloids ajmaline, vincamine, ervatamine, mitragynine, and other indole alkaloids dicentrine and other aporphine alkaloids gonyautoxin paspalitrem and related indoles phalloidine, quinidine, and related quinoline alkaloids sparteine and related quinolizidine alkaloids saxitoxin strychnine tetrodotoxin... 

Aph, flos-aquae Strain NH-1 NH-5 (U.S., New Hampshire) Aphantoxin (neosaxitoxin) Aphantoxin II (saxitoxin) Purine alkaloid MW 315 (neoSTX) MW 299 (STX) 10... 

The main genera responsible for freshwater toxic blooms are Microcystis, Anabaena, Aphanizomenon and Oscillatoria. Toxins produced include 1. anatoxins, alkaloids and peptides of Anabaena 2. the peptide microcystin and related peptides of Microcystis 3. aphantoxins, compounds of Aphanizomenon with properties similar to some paralytic shellfish poisons. Properties of Oscillatoria toxin suggest they are peptides similar to those of Microcystis. Microcystis toxins are peptides (M.W. approx. 1200) which contain three invariant D-amino acids, alanine, erythro-3-methyl aspartic and glutamic acids, two variant L-amino acids, N-methyl dehydro alanine and a 3-amino acid. Individual toxic strains have one or more multiples of this peptide toxin. The one anatoxin characterized is a bicylic secondary amine called anatoxin-a (M.W. 165). The aphantoxin isolated in our laboratory contains two main toxic fractions. On TLC and HPLC the fractions have the same characteristics as saxitoxin and neosaxitoxin. 

Two other suspected alkaloid producing cyanobacteria strains, Anabaena flos-aquae NRC-525-17 and Aphanizomenon flos-aquae NH-5, are now being studied. The toxin of flos-aquae NRC-525-17 (anatoxin-a(s)) is thought to have CNS stimulating properties (7) and that of Aph. flos-aquae NH-5 (aphantoxin) is thought to produce the paralytic shellfish poisons saxitoxin and neosaxitoxin (Fig. 1)... 

The structure of saxitoxin (Figure 6.136) contains a reduced purine ring system, but it is not biosynthetically related to the purine alkaloids... 

A variety of alkaloids bind to or intercalate with DNA or DNA/RNA processing enzymes and affect either transcription or replication (quinine, harmane alkaloids, melinone, berberine), act at the level of DNA and RNA polymerases (vinblastine, coralyne, avicine), inhibit protein synthesis (sparteine, tubulosine, vincrastine, lupanine), attack electron chains (pseudane, capsaicin, solenopsine), disrupt biomembranes and transport processes (berbamine, ellipticine, tetrandrine), and inhibit ion channels and pumps (nitidine, caffeine, saxitoxin). In addition, these natural products attack a variety of other systems that can result in serious biochemical destabilization... 

Cells carefully control the homeostasis of their ion concentrations by the action of ion channels (Na, K , Ca " channels) and throu Na, K -ATPase and Ca -ATPase. These channels and pumps are involved in signal transduction, active transport processes, and neuronal and neuromuscular signaling. Inhibition of transport processes (ion channels, carriers) is achieved by (Table IV) acronycine, ervatamine, harmaline, quinine, reserpine, colchicine, nitidine, salsolinol, sanguinarine, stepholidine, caffeine, sparteine, monocrotaline, steroidal alkaloids, aconitine, capsaicine, cassaine, maitoxin, ochratoxin, palytoxin, pumiliotoxin, saxitoxin, sole-nopsine, and tetrodotoxin. 

Saxitoxin (120), a paralytic shellfish poisoning alkaloid, was obtained from cultures of a red tide dinoflagellate Alexandrium sp. The toxin is also used for studies on ion channels. The biosynthesis of saxitoxin (120) involves arginine as a precursor of the guanidinio groups, whereas the perhydropurine skeleton is derived from Claisen condensation of acetate with arginine. The carbon atom in the side chain is derived from Y-adenosyl methionine. " ... 

Alkaloids which modulate ion channels are tabulated in Table 10. Voltagegated Na+ channels are a target for several steroidal alkaloids, (e.g., batrachotoxinin, samandarine, veratrine, veratridine and zygadenine), indole alkaloids (e.g., ajmaline), aporphines (e.g., dicentrine, liriodenine), quinoline alkaloids (quinine, quinidine), quinolizidine alkaloids (e.g., sparteine, lupanine), and furthermore, for alkaloids present in animals or venoms (e.g., chiriquitoxin, i-conotoxins, dibromosceptrine, gonyauxtoxins, histrionicotoxins, pumiliotoxins, saxitoxin and tetrodotoxin). 

Nitrogen-containing compounds which have been isolated during the past year from sources other than plants and therefore not truly defined as alkaloids are not reviewed. These are saxitoxin (65) from the dinoflagellate Gonyaulax catenella, and leucogenenol (66), a metabolite of Penicillium gilmaniiP ... 

All alkaloids are toxic compounds. However, the degree of toxicity varies widely. Some are extremely toxic compounds, and a good number of these are mild toxicants. The extremely toxic alkaloids include coniine, aconitine, amanitins, chaksine, saxitoxin, and surugatoxin strychnine, nicotine, cytisine, reserpine, and emetine are examples of moderate to highly poisonous alkaloids. Atropine, pilocarpine, quinine, lobeline, ephedrine, and yohimbine are some of the... 

Saxitoxin is an alkaloid of nonplant origin. It is the neurotoxic constituent of dinoflagel-lates (Gonyaulax catenella and G. excavata) the so-called red tide found along the U.S. coast. Shellfish, clams, and scallops consume this and become extremely poisonous for human consumption. 

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