Alkaloids cyanobacteria

Cyanobacterial neurotoxins are small ringed alkaloids and have dramatic effects on various components of vertebrate neurons. They are all water soluble and are synthesized by several cyanobacterial genera (Table 5.1). The most commonly isolated neurotoxins are the paralytic shellfish toxins, although several other potent neurotoxic alkaloids are synthesized by freshwater cyanobacteria (Table 5.1). 

Freshwater cyanobacteria blooms implicated in human and livestock intoxications have been extensively studied. And they have become a serious health problem in recent years. Blooms of marine cyanobacteria are also becoming an increasingly familiar occurrence within the tropical and subtropical regions of the world. Several systematic surveys within Europe and the USA have concluded that the two most commonly isolated groups of cyanotoxins are the alkaloids-neurotoxins and the cyclic peptide hepato-toxins, both of which are destructive to liver cells. Several genera... 

Alkaloid Toxins. Only one alkaloid toxin has been chemically defined from the cyanobacteria. This is the secondary amine, 2-acetyl-9-azabicyclo (4-2-1) non-2-ene, called anatoxin-a. It is isolated from the filamentous strain Anabaena flos-aquae NRG-44-1 (18,19). 

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)... 

In 1999, Rickards et al. reported the isolation of calothrixins A (377) and B (378) from photoautrophic cultures of Calothrix cyanobacteria (345). These two, novel, pentacyclic carbazole alkaloids contain a quinolino[4,3-fc]carbazole-l,4-quinone framework. Calothrixins A and B inhibit the growth of a chloroquin-resistant strain of the malaria parasite P. falciparum and human HeLa cancer cells (345). 

Alkaloid chemistry marine cyanobacteria, 57, 86 (2001) synthetic studies, 50, 377 (1998)... 

Other parts of the northeastern Atlantic are more productive indole alkaloids isolated from bryozoans, seco-steroids from a gorgonian, Gersemia fruticosa, from the White Sea, toxic peptides from brackish-water cyanobacteria, and macrolides from dinoflagellates (Chart 7.8.A/P/PO). 

The teleocidins from terrestrial actinomycetales and the lyngbyatoxins from marine cyanobacteria (Chart 8.3.P) are peptide alkaloids well known for their tumor promoting ability. 

Gerwick WH, Tan LT, Sitachitta N (2001) Nitrogen-Containing Metabolites from Marine Cyanobacteria. In Cordell GA (ed) The Alkaloids, vol 57. Academic, San Diego, p 75... 

Certain strains of cyanobacteria produce toxins. These cyanobacterial toxins can be classified according to their chemical structure or their toxicity. Table 16.1 summarises the characteristics of the main cyanobacterial toxins. Depending on the chemical structure, there are cyclic peptides, alkaloids and lipopolysaccharides. According to the toxic effects, they are classified as ... 

Secondary metabolites with similar structural types and pharmacophoric groups can be seen in several bacteria (where they are often termed antibiotics if they have antimicrobial or cytotoxic properties). Since eukaryotic cells had taken up a-proteobacteria (which became mitochondria) and cyanobacteria (which became chloroplasts), they also inherited a number of genes that encode enzymes for pathways leading to secondary metabolites. Therefore, we may speculate that early plants already had the capacity of building defense compounds and that alkaloids were among the first. Since the numbers and types of herbivores and other enemies have increased within the last 100 million years, angiosperms have had to face more enemies and as a consequence have developed a more complex pattern of defense and signal compounds. 

This chapter reviews the nitrogen-containing neurotoxic compounds produced by cyanobacteria, and follows an earlier review in this series which more broadly covered the alkaloid chemistry of these life forms from the marine environment [3]. A description of the discovery, isolation, structural elucidation, biosynthesis, mechanism of action, structure-activity relationship (SAR), and some aspects of chemical synthesis of cyanobacteria toxins is provided. 

Neurotoxic Alkaloids of Principally Freshwater and Terrestrial Cyanobacteria 141... 

Anatoxin-a is a naturally occurring homotropane alkaloid produced by freshwater cyanobacteria of the genera Anabama (A. flos-ctquae and A. circinalis), Aphanizome-non, Cylindrospermum, Planktothrix, Microcystis aeruginosa [5-7], and Phormidium favosum [8]. Fatal intoxications have typically included cattle and birds [9], and, more recently, dogs [8] and flamingos [10]. 

---