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In silico pharmacophore model for tabun-inhibited acetylcholinesterase (AChE) reactivators: a study of their stereoelectronic properties

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F10%3A00002346" target="_blank" >RIV/60162694:G44__/10:00002346 - isvavai.cz</a>

  • Result on the web

  • DOI - Digital Object Identifier

Alternative languages

  • Result language

    angličtina

  • Original language name

    In silico pharmacophore model for tabun-inhibited acetylcholinesterase (AChE) reactivators: a study of their stereoelectronic properties

  • Original language description

    Organophosphorus (OP) nerve agents that inhibit acetylcholinesterase (AChE; EC 3.1.1.7) function in the nervous system, causing acute intoxication. If untreated, death can result. Inhibited AChE can be reactivated by oximes, antidotes for OP exposure. However, OP intoxication caused by the nerve agent tabun (GA) is particularly resistant to oximes, which poorly reactivate GA-inhibited AChE. In an attempt to develop a rational strategy for the discovery and design of novel reactivators with lower toxicity and increased efficacy in reactivating GA-inhibited AChE, we developed the first in silico pharmacophore model for binding affinity of GA-inhibited AChE from a set of 11 oximes. Oximes were analyzed for stereoelectronic profiles and three-dimensional quantitative structure-activity relationship pharmacophores using ab initio quantum chemical and pharmacophore generation methods. Quantum chemical methods were sequentially used from semiempirical AM1 to hierarchical ab initio calculation

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    FP - Other medical fields

  • OECD FORD branch

Result continuities

  • Project

  • Continuities

    Z - Vyzkumny zamer (s odkazem do CEZ)

Others

  • Publication year

    2010

  • Confidentiality

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

Data specific for result type

  • Name of the periodical

    Chemical Research in Toxicology

  • ISSN

    0893-228X

  • e-ISSN

  • Volume of the periodical

    23

  • Issue of the periodical within the volume

    1

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    11

  • Pages from-to

  • UT code for WoS article

    000273618500005

  • EID of the result in the Scopus database