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HQSAR and molecular docking studies of furanyl derivatives as adenosine A2A receptor antagonists

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Abstract

Structure- and ligand-based computational design strategies were used to understand the molecular requirements of furanyl derivatives 2-(furan-2-yl)-[1,2,4]triazolo[1,5-f]pyrimidin-5-amines (TfPAs), 2-(furan-2-yl)-[1,2,4]triazolo[1,5-a]pyrazin-8-amine (TaPAs), and 2-(furan-2-yl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amines (TTAs) as adenosine A2A receptor (A2AR) antagonists. First, we studied the structure–activity relationship of the selected compounds using hologram quantitative structure–activity relationship (HQSAR) methodology. The best model (training set included 67 compounds) included fragment parameters such as atoms (A), bonds (B), connections (C), and donors/acceptors groups (DA) and had a good q 2 value of 0.776 including size fragments of 7–10 and the hologram length of 199. It also predicted adequately the compounds contained in the test set (10 compounds). In addition, we studied the binding orientations of the higher and less active compounds using flexible molecular docking. We found orientations that are in agreement with previous reports.

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Acknowledgments

A. M. B. thanks to the Universidad de Talca (CBSM) for the continuous support to this investigation, to the postdoctoral Project No. 3150035 (FONDECYT, CHILE). C. M. G. acknowledges support from doctoral fellowship CONICYT-PCHA/Folio 21120214. J. C. acknowledges funds of the Project FONDECYT 1130141.

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  1. Centro de Bioinformática y Simulación Molecular (CBSM), Facultad de Ingeniería, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile

    Camila Muñoz-Gutiérrez, Julio Caballero & Alejandro Morales-Bayuelo

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  1. Camila Muñoz-Gutiérrez
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  2. Julio Caballero
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  3. Alejandro Morales-Bayuelo
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Correspondence to Alejandro Morales-Bayuelo.

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Muñoz-Gutiérrez, C., Caballero, J. & Morales-Bayuelo, A. HQSAR and molecular docking studies of furanyl derivatives as adenosine A2A receptor antagonists. Med Chem Res 25, 1316–1328 (2016). https://doi.org/10.1007/s00044-016-1575-1

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