Abstract
Adenosine regulates tissue function by activating four G-protein-coupled adenosine receptors (ARs). Selective agonists and antagonists for \(\hbox {A}_{3}\) ARs have been investigated for the treatment of a variety of immune disorders, cancer, brain, and heart ischemic conditions. We herein present a QSAR study based on a Topological sub-structural molecular design (TOPS-MODE) approach, intended to predict the \(\hbox {A}_{3}\) ARs of a diverse dataset of 124 (94 training set/ 30 prediction set) adenosine derivatives. The final model showed good fit and predictive capability, displaying 85.1 % of the experimental variance. The TOPS-MODE approach afforded a better understanding and interpretation of the developed model based on the useful information extracted from the analysis of the contribution of different molecular fragments to the affinity.
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Acknowledgments
The authors acknowledge the Xunta de Galicia (PGIDIT07PXIB and INCITE08ENA314019ES) and the Portuguese Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BPD/63946/2009) for financial support. We also thank the owners of the MODESLAB for free donation of this software to our investigation group.
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Saíz-Urra, L., Teijeira, M., Rivero-Buceta, V. et al. Topological sub-structural molecular design (TOPS-MODE): a useful tool to explore key fragments of human \(\mathbf{A}_{3}\) adenosine receptor ligands. Mol Divers 20, 55–76 (2016). https://doi.org/10.1007/s11030-015-9617-z
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DOI: https://doi.org/10.1007/s11030-015-9617-z