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Molecular modeling of acetylcholinesterase interaction with irreversible and reversible organophosphorus inhibitors

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Abstract

Three-dimensional (3D) Quantitative Structure-Activity Relationship models were designed for irreversible and reversible acetylcholinesterase inhibitors by molecular modeling methods. In the case of irreversible inhibitors CoMFA (comparative molecular fields analysis) or CoMSIA (comparative molecular similarity indices analysis) descriptors in combination with HYBOT 3D fields provide more statistically valid 3D-QSAR models. This indicates importance of donor-acceptor interactions for irreversible acetylcholinesterase inhibition. In the case of reversible organophosphorous inhibitors a good quality model for structure-activity relationships was developed using CoMFA fields. The obtained models have good predictive power and can be used for estimation of inhibitory activity of new organophosphorous compounds that in turn correlates with toxicity of these compounds.

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Authors and Affiliations

  1. Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119121, Russia

    O. V. Tikhonova & V. S. Skvortsov

  2. Institute of Phisiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Moscow region, Russia

    O. V. Tikhonova, V. S. Skvortsov & O. A. Raevsky

Authors
  1. O. V. Tikhonova
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  2. V. S. Skvortsov
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  3. O. A. Raevsky
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Correspondence to O. V. Tikhonova.

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Original Russian Text © O.V. Tikhonova, V.S. Skvortsov, O.A. Raevsky, 2010, published in Biomeditsinskaya Khimiya.

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Tikhonova, O.V., Skvortsov, V.S. & Raevsky, O.A. Molecular modeling of acetylcholinesterase interaction with irreversible and reversible organophosphorus inhibitors. Biochem. Moscow Suppl. Ser. B 4, 342–352 (2010). https://doi.org/10.1134/S1990750810040049

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  • DOI: https://doi.org/10.1134/S1990750810040049

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