Selectivity of Spiroimine Phycotoxins Toward Nicotinic Acetylcholine Receptors

摘要: Spiroimine phycotoxins are macrocyclic marine neurotoxins that found in contaminated shellfish [1,2]. Most of them strong antagonists nicotinic acetylcholine receptors (nAChRs), with high affinity and selectivity on different subtypes [3].In this study, we used ligand- structure-based molecular modeling methods to identify the residues controlling representative members toxins family toward nAChRs. The conformation flexibility ring was an essential requirement for correct positioning ligands binding site [4,5]. pertinence approaches generate conformers will be discussed.Our results guide further structural modifications within spiroimine family, design a new generation synthetic derivatives better activity profiles.1. Molgo et al. “Cyclic imine toxins: chemistry, origin, metabolism, pharmacology, toxicology, detection” “Seafood freshwater toxins. Pharmacology physiology detection”, CRC Press, 2014, pp 951-990.2. acting muscarinic receptors” “Toxins biologically active compounds from microalgae”, 116-146.3. al., Exp. Opin. Drug Discov. 2013, 8, 1203.4. Araoz J. Am. Chem. Soc. 2011, 133, 10499-10511.5. Toxicol. Sci. 2015, 147, 156-167.