Flexibility in the Molecular Design of Acetylcholinesterase Reactivators: Probing Representative Conformations by Chemometric Techniques and Docking/QM Calculations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F16%3A50004689" target="_blank" >RIV/62690094:18450/16:50004689 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.2174/1570180812666150918191550" target="_blank" >http://dx.doi.org/10.2174/1570180812666150918191550</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570180812666150918191550" target="_blank" >10.2174/1570180812666150918191550</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Flexibility in the Molecular Design of Acetylcholinesterase Reactivators: Probing Representative Conformations by Chemometric Techniques and Docking/QM Calculations

Popis výsledku v původním jazyce

Neurotoxic organophosphate compounds (OP) are toxic and acetylcholinesterase (AChE) inhibitors widely used as insecticides and pesticides in agriculture. This is a key enzyme in the search for new strategies for poisoning treatment by means of pesticides and insecticides. The standard OP intoxication treatment involves the administration of an anticholinergic to reduce spasms and convulsion as well as a cationic oxime capable of removing the OP compounds inside the AChE active site to reactivate the enzyme. In this paper, a theoretical strategy combining docking(MM), chemometric analysis and QM calculations was employed to check out the association and kinetic reactivation coefficients associated to oximes, confronting in vitro the data found in the literature before. The docking results were selected by means of the principal components analysis and submitted to QM calculations. The calculated thermodynamics and kinetics parameters revealed a good correspondence between the calculated intermolecular energy values of the oximes and experimental results, reinforcing the theoretical findings and confirming the theoretical strategy used as a suitable tool for the prediction of kinetic and thermodynamics parameters, which would be able to collaborate with the design of new oximes more effective.

Název v anglickém jazyce

Flexibility in the Molecular Design of Acetylcholinesterase Reactivators: Probing Representative Conformations by Chemometric Techniques and Docking/QM Calculations

Popis výsledku anglicky

Neurotoxic organophosphate compounds (OP) are toxic and acetylcholinesterase (AChE) inhibitors widely used as insecticides and pesticides in agriculture. This is a key enzyme in the search for new strategies for poisoning treatment by means of pesticides and insecticides. The standard OP intoxication treatment involves the administration of an anticholinergic to reduce spasms and convulsion as well as a cationic oxime capable of removing the OP compounds inside the AChE active site to reactivate the enzyme. In this paper, a theoretical strategy combining docking(MM), chemometric analysis and QM calculations was employed to check out the association and kinetic reactivation coefficients associated to oximes, confronting in vitro the data found in the literature before. The docking results were selected by means of the principal components analysis and submitted to QM calculations. The calculated thermodynamics and kinetics parameters revealed a good correspondence between the calculated intermolecular energy values of the oximes and experimental results, reinforcing the theoretical findings and confirming the theoretical strategy used as a suitable tool for the prediction of kinetic and thermodynamics parameters, which would be able to collaborate with the design of new oximes more effective.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Letters in drug design &amp; discovery

ISSN

1570-1808

e-ISSN

—

Svazek periodika

13

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

12

Strana od-do

360-371

Kód UT WoS článku

000374883700002

EID výsledku v databázi Scopus

2-s2.0-84966397040