Pyridoxal oxime derivative potency to reactivate cholinesterases inhibited by organophosphorus compounds

Bušić, Valentina; Katalinić, Maja; Šinko, Goran; Kovarik, Zrinka; Gašo-Sokač, Dajana

doi:10.1016/j.toxlet.2016.09.015

Cited by 16 publications

(14 citation statements)

References 43 publications

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“…For all of the compounds in this study, K i was measured by our laboratory and published previously ( Tables 1 and S3 , Fig. 1 ) ( Bosak et al, 2019 , Bosak et al, 2017 , Bušić et al, 2016 , Katalinić et al, 2010 , Kovarik et al, 2008 , Maček Hrvat et al, 2020 , Maraković et al, 2020 , Maraković et al, 2016 , Šinko et al, 2010 , Zandona et al, 2020 ). The assay used for the AChE activity measurement was based on the Ellman method ( Ellman et al, 1961 ), with standardized activity measurement regarding enzyme, substrate and inhibitor concentrations ( Eyer et al, 2003 , Reiner et al, 2000 ).…”

Section: Introductionmentioning

confidence: 92%

Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase

Miličević

Šinko

2022

Saudi Pharmaceutical Journal

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Section: Introductionmentioning

confidence: 92%

Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase

Miličević

Šinko

2022

Saudi Pharmaceutical Journal

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“…Interestingly, BChE has a network of aromatic residues in the active site. This network, rich in π-electrons, includes Trp82, the residue involved in the mechanism of substrate hydrolysis, and the surrounding four additional residues Tyr128, Tyr332, Trp430, and Tyr440 [30]. Close to this network are two also relevant aromatic residues: Trp231 and Phe329.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and In Vitro Screening of Novel Heterocyclic β-d-Gluco- and β-d-Galactoconjugates as Butyrylcholinesterase Inhibitors

et al. 2019

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The development of selective butyrylcholinesterase (BChE) inhibitors may improve the treatment of Alzheimer’s disease by increasing lower synaptic levels of the neurotransmitter acetylcholine, which is hydrolysed by acetylcholinesterase, as well as by overexpressed BChE. An increase in the synaptic levels of acetylcholine leads to normal cholinergic neurotransmission and improved cognitive functions. A series of 14 novel heterocyclic β-d-gluco- and β-d-galactoconjugates were designed and screened for inhibitory activity against BChE. In the kinetic studies, 4 out of 14 compounds showed an inhibitory effect towards BChE, with benzimidazolium and 1-benzylbenzimidazolium substituted β-d-gluco- and β-d-galacto-derivatives in a 10–50 micromolar range. The analysis performed by molecular modelling indicated key residues of the BChE active site, which contributed to a higher affinity toward the selected compounds. Sugar moiety in the inhibitor should enable better blood–brain barrier permeability, and thus increase bioavailability in the central nervous system of these compounds.

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“…However, combining BChE with standard pyridinium oximes proved to be ineffective, as these oximes are mainly AChE reactivators ( 191 ). Research has therefore looked into several promising newly synthesised oximes that reactivate phosphylated BChE ( 70 , 191 , 192 , 193 , 194 , 195 , 196 , 197 ), and some progress has been achieved with new classes of BChE reactivators like quaternary benzaldoximes ( 192 ) imidazole aldoximes ( 193 , 195 ), cinchona derivatives oximes ( 196 ), and hydroxypyridine aldoximes ( 87 , 90 ). Furthermore, members of the oxime libraries that can cross the BBB were found to effectively reactivate sarin-, cyclosarin-, VX-, and paraoxon-inhibited BChE and AChE ( 91 , 108 , 193 ).…”

Section: Protection Of Native Ache From Inhibitionmentioning

confidence: 99%

Counteracting poisoning with chemical warfare nerve agents

Hrvat

Kovarik

2020

Archives of Industrial Hygiene and Toxicology

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Phosphylation of the pivotal enzyme acetylcholinesterase (AChE) by nerve agents (NAs) leads to irreversible inhibition of the enzyme and accumulation of neurotransmitter acetylcholine, which induces cholinergic crisis, that is, overstimulation of muscarinic and nicotinic membrane receptors in the central and peripheral nervous system. In severe cases, subsequent desensitisation of the receptors results in hypoxia, vasodepression, and respiratory arrest, followed by death. Prompt action is therefore critical to improve the chances of victim’s survival and recovery. Standard therapy of NA poisoning generally involves administration of anticholinergic atropine and an oxime reactivator of phosphylated AChE. Anticholinesterase compounds or NA bioscavengers can also be applied to preserve native AChE from inhibition. With this review of 70 years of research we aim to present current and potential approaches to counteracting NA poisoning.

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Pyridoxal oxime derivative potency to reactivate cholinesterases inhibited by organophosphorus compounds

Cited by 16 publications

References 43 publications

Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase

Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase

Synthesis and In Vitro Screening of Novel Heterocyclic β-d-Gluco- and β-d-Galactoconjugates as Butyrylcholinesterase Inhibitors

Counteracting poisoning with chemical warfare nerve agents

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