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Latest QSAR study of adenosine A\(_{\mathrm{2B}}\) receptor affinity of xanthines and deazaxanthines

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Abstract

Adenosine, a widespread and endogenous nucleoside that acts as a powerful neuromodulator in the nervous system, is a promising therapeutic target in a wide range of conditions. The structural similarity between xanthine derivatives and neurotransmitter adenosine has led to the derivatives of the heterocyclic ring being among the most abundant chemical classes of ligand antagonists of adenosine receptor subtypes. Small changes in the xanthine scaffold have resulted in a wide array of adenosine receptor antagonists. In this work, we developed a QSAR model for the \(\hbox {A}_{\mathrm{2B}}\) subtype, which is, as yet, not well characterized, with two purposes in mind: to predict adenosine \(\hbox {A}_{\mathrm{2B}}\) antagonist activity and to offer a substructural interpretation of this group of xanthines. The QSAR model provided good classifications of both the test and external sets. In addition, most of the contributions to adenosine \(\hbox {A}_{\mathrm{2B}}\) receptor affinity derived by subfragmentation of the molecules in the training set agree with the relationships observed in the literature. These two factors mean that this QSAR ensemble could be used as a model to predict future adenosine \(\hbox {A}_{\mathrm{2B}}\) antagonist candidates.

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Acknowledgments

This work was partially supported by the Catholic University of San Antonio (PMAFI/08/12) and by the Xunta de Galicia (CN2012/184), by the Fundación Séneca de la Región de Murcia under Project 18946/JLI/13, and by the Nils Coordinated Mobility under grant 012-ABEL-CM-2014A, in part financed by the European Regional Development Fund (ERDF).

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Authors and Affiliations

  1. Bioinformatics and High Performance Computing Research Group, Computer Science Department, Universidad Católica de Murcia, 30107, Guadalupe, Murcia, Spain

    Alfonso Pérez-Garrido & Horacio Pérez-Sánchez

  2. Departamento de Tecnología de la Alimentación y Nutrición, Universidad Católica de Murcia, 30107, Guadalupe, Murcia, Spain

    Alfonso Pérez-Garrido

  3. Departamento de Química Orgánica, Universidad de Vigo, 36320, Vigo, Pontevedra, Spain

    Virginia Rivero-Buceta & Marta Teijeira Bautista

  4. Instituto de Investigación Biomédica (IVIB), Universidade de Vigo, Vigo, Spain

    Virginia Rivero-Buceta & Marta Teijeira Bautista

  5. Computing Technology Department, University of Alicante, Ap. 99, E03080, Alicante, Spain

    Gaspar Cano

  6. Bioinformatics Centre, Biotech Park, Sector G. Janpakipuram, Lucknow, 226021, India

    Sanjay Kumar

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  1. Alfonso Pérez-Garrido
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Pérez-Garrido, A., Rivero-Buceta, V., Cano, G. et al. Latest QSAR study of adenosine A\(_{\mathrm{2B}}\) receptor affinity of xanthines and deazaxanthines. Mol Divers 19, 975–989 (2015). https://doi.org/10.1007/s11030-015-9608-0

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