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.

Organocatalysis in aqueous media

“…80,82 Additionally, the nucleophilic catalysis of 28 (pKa 6.9) is pH-dependent and favours basic conditions, as more imidazole free base species are present. 95 Besides the well-established hydrolysis of activated esters it was shown that imidazole and/or histidine can catalyse other reaction types: the aldol reaction (enamine-mediated, described above), hydrolysis of N-acetylserinamide, RNA cleavage, thioester hydrolysis, amongst others. 95 Additionally, several studies showed effective catalysts designs with imidazole/ histidine residues as part of a nanoparticle 96 , polymer 97,98 or protein 93,[99][100][101] .…”

“…95 Besides the well-established hydrolysis of activated esters it was shown that imidazole and/or histidine can catalyse other reaction types: the aldol reaction (enamine-mediated, described above), hydrolysis of N-acetylserinamide, RNA cleavage, thioester hydrolysis, amongst others. 95 Additionally, several studies showed effective catalysts designs with imidazole/ histidine residues as part of a nanoparticle 96 , polymer 97,98 or protein 93,[99][100][101] . Remarkably, in 2000, Chen described Ser-His as a minimalistic enzyme for amide hydrolysis 102 , yet follow-up research proved Ser-His is only able to catalyse activated ester hydrolysis (similar to imidazole activity).…”

Facile Synthesis of Unsymmetrical Trialkoxysilanols: (RO)2(R′O)SiOH

“…Inspired by reports of imidazole promoted substitution reactions, we find that replacing pyridine with imidazole as base greatly improves the yield of both Steps IIb and III . The reaction of 1 with HOCMe 2 (vinyl) at 50 °C for 18 h in the presence of imidazole gives 71% of the desired product ( 2c ).…”

3D-Molecular Modeling, Antibacterial Activity and Molecular Docking Studies of Some Imidazole Derivatives

“…Heterocycles play an important role in drug discovery and medicinal chemistry [1] including the nitrogen-containing heterocycles [2]. Imidazole containing natural products are gaining much interest due to their potent bioactivity and hence, promising agents in drug discovery [3,4] involving anti-bacterial, anti-fungal, anti-cancer, anti-oxidant and antiparkinson activities [5][6][7]. For example, Pretomanid and Delamanid were confirmed for their potent anti-TB activity [8][9][10].…”