Mechanistic studies of new oximes reactivators of human butyryl cholinesterase inhibited by cyclosarin and sarin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18450%2F17%3A50005092" target="_blank" >RIV/62690094:18450/17:50005092 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1080/07391102.2016.1178173" target="_blank" >http://dx.doi.org/10.1080/07391102.2016.1178173</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07391102.2016.1178173" target="_blank" >10.1080/07391102.2016.1178173</a>

Result language

angličtina

Original language name

Mechanistic studies of new oximes reactivators of human butyryl cholinesterase inhibited by cyclosarin and sarin

Original language description

Butyryl cholinesterase (BChE) has been seen as a key enzyme in the search for new strategies in the treatment of poisoning by organophosphates (OPs), since human BChE (HssBChE), complexed with the appropriate oxime, can be a suitable scavenger and deactivator for OPs in the blood stream. However, the efficacy of HssBChE is limited by its strict stoichiometric scavenging, slow reactivation, and propensity for aging. The improvement of the reactivation rate by new and more efficient oximes could contribute to mitigate this problem and increase the HssBChE efficiency as scavenger. Several oximes have been synthesized and tested with this goal, some with promising results, but the mechanistic aspects of the reactivation reaction are not fully understood yet. In order to better investigate this mechanism, docking and mixed quantum and molecular mechanics combined with principal components analysis were performed here to evaluate the capacity of reactivation and determine the preferred route for the reactivation reaction of two new oximes on HssBChE inhibited by the neurotoxic agents cyclosarin and sarin. Plots of potential energies were calculated and all the transition states of the reactional mechanism were determined. Our results showed a good correlation with experimental data and pointed to the most efficient oxime with both OPs. The protocol used could be a suitable tool for a preliminary evaluation of the HssBChE reactivation rates by new oximes.

Czech name

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Czech description

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Type

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

CEP classification

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OECD FORD branch

10609 - Biochemical research methods

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

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

Name of the periodical

Journal of biomolecular structure and dynamics

ISSN

0739-1102

e-ISSN

—

Volume of the periodical

35

Issue of the periodical within the volume

6

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

1272-1282

UT code for WoS article

000400177700009

EID of the result in the Scopus database

2-s2.0-84976303066