Combined QSAR studies of inhibitor properties of O-phosphorylated oximes toward serine esterases involved in neurotoxicity, drug metabolism and Alzheimer's disease

SAR and QSAR in Environmental Research
G F MakhaevaN S Zefirov

Abstract

Oxime reactivation of serine esterases (EOHs) inhibited by organophosphorus (OP) compounds can produce O-phosphorylated oximes (POXs). Such oxime derivatives are of interest, because some of them can have greater anti-EOH potencies than the OP inhibitors from which they were derived. Accordingly, inhibitor properties of 58 POXs against four EOHs, along with pair-wise selectivities between them, have been analysed using different QSAR approaches. EOHs (with their abbreviations and consequences of inhibition in parentheses) comprised acetylcholinesterase (AChE: acute neurotoxicity; cognition enhancement), butyrylcholinesterase (BChE: inhibition of drug metabolism or stoichiometric scavenging of EOH inhibitors; cognition enhancement), carboxylesterase (CaE: inhibition of drug metabolism or stoichiometric scavenging of EOH inhibitors), and neuropathy target esterase (NTE: delayed neurotoxicity). QSAR techniques encompassed linear regression and backpropagation neural networks in conjunction with fragmental descriptors containing labelled atoms, Molecular Field Topology Analysis (MFTA), Comparative Molecular Similarity Index Analysis (CoMSIA), and molecular modelling. All methods provided mostly consistent and complementary informat...Continue Reading

References

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Dec 29, 2009·Chemico-biological Interactions·G F MakhaevaR J Richardson
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Apr 6, 2011·The Journal of Biological Chemistry·Rakesh K SitPalmer Taylor
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May 9, 2012·Doklady. Biochemistry and Biophysics·E V RadchenkoN S Zefirov

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Citations

Aug 27, 2013·Doklady. Biochemistry and Biophysics·G F MakhaevaI V Martynov
Apr 24, 2014·Expert Opinion on Drug Discovery·Pravin Ambure, Kunal Roy
Nov 6, 2012·Chemico-biological Interactions·Galina F MakhaevaRudy J Richardson
Jan 9, 2019·Pharmaceutical Research·Peter Bloomingdale, Donald E Mager
Jan 25, 2019·Current Topics in Medicinal Chemistry·Alexander V DmitrievVladimir V Poroikov
Sep 17, 2019·Analytica Chimica Acta·Xiao Hu, Cerasela Zoica Dinu

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