title: Topological sub-structural molecular design (TOPS-MODE): a useful tool to explore key fragments of human A3 adenosine receptor ligands.
abstract: Adenosine regulates tissue function by activating four G-protein-coupled adenosine receptors (ARs). Selective agonists and antagonists for A3 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 A3 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.
authors.affiliation: Laboratory for Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, 3000, Leuven, Belgium.
authors.forename: Liane
authors.initials: L
authors.lastname: Saíz-Urra
authors.affiliation: Departamento de Química Orgánica. Facultade de Química, Universidade de Vigo, 36310, Vigo, Spain. qomaca@uvigo.es.|Instituto de Investigación Biomédica (IVIB), Universidade de Vigo, 36310, Vigo, Spain. qomaca@uvigo.es.
authors.forename: Marta
authors.identifier: http://orcid.org/0000-0001-9833-134X
authors.initials: M
authors.lastname: Teijeira
authors.affiliation: Departamento de Química Orgánica. Facultade de Química, Universidade de Vigo, 36310, Vigo, Spain.|Instituto de Investigación Biomédica (IVIB), Universidade de Vigo, 36310, Vigo, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Rivero-Buceta
authors.affiliation: CIQ, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal.|Centro de Bioactivos Químicos, Universidad Central "Marta Abreu" de Las Villas, 54830, Santa Clara, Villa Clara, Cuba.
authors.forename: Aliuska Morales
authors.initials: AM
authors.lastname: Helguera
authors.affiliation: Departamento de Química Orgánica. Facultade de Química, Universidade de Vigo, 36310, Vigo, Spain.|Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Celeiro
authors.affiliation: Departamento de Química Orgánica. Facultade de Química, Universidade de Vigo, 36310, Vigo, Spain.|Instituto de Investigación Biomédica (IVIB), Universidade de Vigo, 36310, Vigo, Spain.
authors.forename: Ma Carmen
authors.initials: MC
authors.lastname: Terán
authors.affiliation: Departamento de Química Orgánica. Facultade de Química, Universidade de Vigo, 36310, Vigo, Spain.|Instituto de Investigación Biomédica (IVIB), Universidade de Vigo, 36310, Vigo, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Besada
authors.affiliation: CIQ, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007, Porto, Portugal.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Borges
mesh_terms: D058909:Adenosine A3 Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D043684:Receptor, Adenosine A3 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D043684:Receptor, Adenosine A3
keywords: Fragment contributions; QSAR; TOPS-MODE, Ddrug discovery; adenosine receptor agonist