title: Cholinesterase-like organocatalysis by imidazole and imidazole-bearing molecules.
abstract: Organocatalysis, which is mostly explored for its new potential industrial applications, also represents a chemical event involved in endogenous processes. In the present study, we provide the first evidence that imidazole and imidazole derivatives have cholinesterase-like properties since they can accelerate the hydrolysis of acetylthiocholine and propionylthiocholine in a concentration-dependent manner. The natural imidazole-containing molecules as L-histidine and histamine show a catalytic activity, comparable to that of imidazole itself, whereas synthetic molecules, as cimetidine and clonidine, were less active. In the experimental conditions used, the reaction progress curves were sigmoidal and the rational of such unexpected behavior as well as the mechanism of catalysis is discussed. Although indirectly, findings of the present study suggests that imidazolic compounds may interfere with the homeostasis of the cholinergic system in vivo.
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Nieri
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Carpi
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fogli
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Polini
authors.affiliation: Department of Pharmacy, University of Pisa, Pisa, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Breschi
authors.affiliation: Department of Veterinary Sciences, University of Pisa, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Podestà
mesh_terms: D002384:Catalysis; D002802:Cholinesterases / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006632:Histamine / Q000737:chemistry / Q000494:pharmacology*; D006639:Histidine / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D006639:Histidine; C029899:imidazole; D006632:Histamine; D002802:Cholinesterases; C023439:4-methylimidazole; C518739:1-ethyl-3-methylimidazolium