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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30108 - Toxicology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Letters in drug design &amp; discovery

ISSN

1570-1808

e-ISSN

—

Volume of the periodical

13

Issue of the periodical within the volume

5

Country of publishing house

AE - UNITED ARAB EMIRATES

Number of pages

12

Pages from-to

360-371

UT code for WoS article

000374883700002

EID of the result in the Scopus database

2-s2.0-84966397040