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Topological sub-structural molecular design (TOPS-MODE): a useful tool to explore key fragments of human \(\mathbf{A}_{3}\) adenosine receptor ligands

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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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Authors and Affiliations

  1. Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium

    Liane Saíz-Urra

  2. Departamento de Química Orgánica. Facultade de Química, Universidade de Vigo, 36310, Vigo, Spain

    Marta Teijeira, Virginia Rivero-Buceta, Maria Celeiro, Mª Carmen Terán & Pedro Besada

  3. Instituto de Investigación Biomédica (IVIB), Universidade de Vigo, 36310, Vigo, Spain

    Marta Teijeira, Virginia Rivero-Buceta, Mª Carmen Terán & Pedro Besada

  4. CIQ, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal

    Aliuska Morales Helguera & Fernanda Borges

  5. Centro de Bioactivos Químicos, Universidad Central “Marta Abreu” de Las Villas, 54830, Santa Clara, Villa Clara, Cuba

    Aliuska Morales Helguera

  6. Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain

    Maria Celeiro

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  1. Liane Saíz-Urra
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Correspondence to Marta Teijeira.

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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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