Research Article: Insights into the Molecular Requirements for the Anti-obesity Activity of a Series of CB1 Ligands

Authors

  • Karen C. Weber,

    1. Departamento de Química, Universidade Federal da Paraíba, C.P. 5093, 58051-970 João Pessoa, PB, Brazil
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  • Emmanuela F. De Lima,

    1. Scuola Internazionale Superiore di Studi Avanzati/International School for Advanced Studies, SISSA (ISAS), via Beirut 2-4, 34151 Trieste, Italy
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  • Paula H. De Mello,

    1. Universidade Federal do ABC, Rua Santa Adélia, 166, Bangu, 09210-170 Santo André, SP, Brazil
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  • Albérico B. F. Da Silva,

    1. Instituto de Química de São Carlos, Universidade de São Paulo, Av. Trabalhador São-Carlense 400, C.P. 780, 13560-970 São Carlos, SP, Brazil
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  • Káthia M. Honório

    Corresponding author
    1. Universidade Federal do ABC, Rua Santa Adélia, 166, Bangu, 09210-170 Santo André, SP, Brazil
    2. Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, Av. Arlindo Bettio, 1000, 03828-000 São Paulo, SP, Brazil
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Corresponding author: Káthia M. Honório, kmhonorio@usp.br

Abstract

Two-dimensional and 3D quantitative structure–activity relationships studies were performed on a series of diarylpyridines that acts as cannabinoid receptor ligands by means of hologram quantitative structure–activity relationships and comparative molecular field analysis methods. The quantitative structure–activity relationships models were built using a data set of 52 CB1 ligands that can be used as anti-obesity agents. Significant correlation coefficients (hologram quantitative structure–activity relationships: r 2 = 0.91, q 2 = 0.78; comparative molecular field analysis: r 2 = 0.98, q 2 = 0.77) were obtained, indicating the potential of these 2D and 3D models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted (calculated) values are in good agreement with the experimental results. The final quantitative structure–activity relationships models, along with the information obtained from 2D contribution maps and 3D contour maps, obtained in this study are useful tools for the design of novel CB1 ligands with improved anti-obesity potency.

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