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CoMFA validation of the superposition of six classes of compounds which block GABA receptors non-competitively

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Summary

Thirty-six compounds, representing six different structural classes of insecticides which are known to act at the γ-aminobutyric acid receptor/chloride ionophore, have been superimposed by methods which maximise the commonality of steric and electrostatic fields. Maximal steric and electrostatic alignment was derived by pairwise comparisons of the different chemical classes with picrotoxinin. To test the validity of the combined superposition, a Comparative Molecular Field Analysis (CoMFA) was carried out within SYBYL, using recently published in vivo and in vitro binding data for insecticides. The resultant partial least-squares (PLS) analysis of sampled steric and electrostatic fields showed a significant statistical correlation with the published biological data. The predictive model obtained was shown to have a greater than 95% chance of significance.

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Authors and Affiliations

  1. Department of Chemistry, Roussel Uclaf Environmental Health, HP4 2DY, Berkhamsted, U.K.

    Julie A. Calder, John A. Wyatt & David A. Frenkel

  2. Pesticide Chemistry and Toxicology Laboratory, Department of Entomological Sciences, University of California, 94720, Berkeley, CA, U.S.A.

    John E. Casida

Authors
  1. Julie A. Calder
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  2. John A. Wyatt
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  3. David A. Frenkel
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  4. John E. Casida
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Calder, J.A., Wyatt, J.A., Frenkel, D.A. et al. CoMFA validation of the superposition of six classes of compounds which block GABA receptors non-competitively. J Computer-Aided Mol Des 7, 45–60 (1993). https://doi.org/10.1007/BF00141574

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  • DOI: https://doi.org/10.1007/BF00141574

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