PMID: 9630015Jun 18, 1998Paper

Quinuclidinium-imidazolium compounds: synthesis, mode of interaction with acetylcholinesterase and effect upon Soman intoxicated mice

Archives of Toxicology
Vera Simeon-RudolfSrdanka Tomić

Abstract

Four compounds were prepared: 3-oxo-1-methylquinuclidinium iodide (I), 2-hydroxyiminomethyl-1,3-dimethylimidazolium iodide (II) and two conjugates of I and II linked by -(CH2)3- (III) and -CH2-O-CH2- (IV). The aim was to evaluate separately the properties of I and II as opposed to III and IV, which contain both moieties in the same molecule. All four compounds were reversible inhibitors of acetylcholinesterase (AChE; EC 3.1.1.7). The enzyme/inhibitor dissociation constants for the catalytic site ranged from 0.073 mM (II) to 1.6 mM (I). The dissociation constant of I for the allosteric (substrate inhibition) site was 4.8 mM. Possible binding of the other compounds to the allosteric site could not be measured because II, III and IV reacted with the substrate acetylthiocholine (ATCh) and at high ATCh concentrations the non-enzymic reaction interfered with the enzymic hydrolysis of ATCh. The rate constants for the non-enzymic ATCh hydrolysis were between 23 and 37 l/mol per min. All four compounds protected AChE against phosphorylation by Soman and VX. The protective index (PI) of I (calculated from binding of I to both, catalytic and allosteric sites in AChE) agreed with the measured PI; this confirms that allosteric binding contr...Continue Reading

Citations

Jun 20, 2006·Neurotoxicity Research·Lucie BartosovaDaniel Jun
Oct 5, 2007·Arhiv za higijenu rada i toksikologiju·Elsa ReinerVera Simeon-Rudolf
Apr 7, 2006·Biochemical and Biophysical Research Communications·Zrinka KovarikPalmer Taylor
Sep 20, 2006·Toxicology·Ana Lucić VrdoljakZrinka Kovarik
Nov 1, 2007·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Renata Odzak, Srdjanka Tomic
Sep 23, 2016·Toxicology and Applied Pharmacology·Maja KatalinićZrinka Kovarik
Mar 15, 2006·Bioorganic Chemistry·Renata Odzak, Srdanka Tomić
Mar 20, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Suzana BerendBozica Radić
May 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mirjana SkočibušićInes Primožič
Apr 4, 2021·Pharmaceutics·Ana MatoševićTomica Hrenar

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