Cyclic Imines: Chemistry and Mechanism of Action: A Review

• Published in: Chemical research in toxicology Vol. 24; no. 11; pp. 1817 - 1829
• Main Authors: Otero, Alberto, Chapela, María-José, Atanassova, Miroslava, Vieites, Juan M, Cabado, Ana G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.11.2011
• Subjects: Animals; Binding Sites; Biological Assay; Cell Survival - drug effects; Food Contamination; Heterocyclic Compounds, 3-Ring - chemistry; Heterocyclic Compounds, 3-Ring - metabolism; Heterocyclic Compounds, 3-Ring - toxicity; Humans; Hydrocarbons, Cyclic - chemistry; Hydrocarbons, Cyclic - metabolism; Hydrocarbons, Cyclic - toxicity; Imines - chemistry; Imines - metabolism; Imines - toxicity; Injections, Intraperitoneal; Marine Toxins - chemistry; Marine Toxins - metabolism; Marine Toxins - toxicity; Mice; Microalgae - chemistry; Muscarinic Antagonists - chemistry; Muscarinic Antagonists - metabolism; Muscarinic Antagonists - toxicity; Nicotinic Antagonists - chemistry; Nicotinic Antagonists - metabolism; Nicotinic Antagonists - toxicity; Protein Binding; Pyrans - chemistry; Pyrans - metabolism; Pyrans - toxicity; Receptors, Muscarinic - metabolism; Receptors, Nicotinic - metabolism; Shellfish - toxicity; Shellfish Poisoning - metabolism; Shellfish Poisoning - physiopathology; Spiro Compounds - chemistry; Spiro Compounds - metabolism; Spiro Compounds - toxicity; Structure-Activity Relationship
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx200182m

In recent years, there has been an increase in the production of shellfish and in global demand for seafood as nutritious and healthy food. Unfortunately, a significant number of incidences of shellfish poisoning occur worldwide, and microalgae that produce phycotoxins are responsible for most of these. Phycotoxins include several groups of small to medium sized natural products with molecular masses ranging from 300 to over 3000 Da. Cyclic imines (CIs) are a recently discovered group of marine biotoxins characterized by their fast acting toxicity, inducing a characteristic rapid death in the intraperitoneal mouse bioassay. These toxins are macrocyclic compounds with imine (carbon–nitrogen double bond) and spiro-linked ether moieties. They are grouped together due to the imino group functioning as their common pharmacore and due to the similarities in their intraperitoneal toxicity in mice. Spirolides (SPXs) are the largest group of CIs cyclic imines that together with gymnodimines (GYMs) are best characterized. Although the amount of cyclic imines in shellfish is not regulated and these substances have not been categorically linked to human intoxication, they trigger high intraperitoneal toxicity in rodents. In this review, the corresponding chemical structures of each member of the CIs and their derivatives are reviewed as well as all the data accumulated on their mechanism of action at cellular level.