Anales RANF

S18-03 EVOLUTIONARY APPROACHES FOR ADENOSINE RECEPTORS MODULATION E. Sotelo 1 1 . University of Santiago de Compostela, Spain. The purine nucleoside adenosine is present in all body fluids . In addition to its well- known role as genetic code building block and energy transfer processes, adenosine participates in diverse biochemical events. It has a cytoprotective function, while its extracellular accumulation contributes to the regulation of inflammation, immunity and tissue repair. Adenosine exerts its action by interacting with P 1 receptors, a family of highly conserved receptor subtypes that belong to the family of seven transmembrane G-protein-coupled receptors. 1 The four adenosine receptors (A 1 , A 2A , A 2B and A 3 ) have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. 1 Recent advances on the physiology, pharmacology and the structural and molecular biology of adenosine and its receptors has provided solid evidences that supports the ability of adenosine to regulate diverse physiopathological events. These findings, along with the identification of potent and selective ligands, embrace the emergence of conceptually novel therapeutic strategies to address significant unmet medical needs. 3 For several years we have been involved in a medicinal chemistry program aimed to develop novel A 1 , A 2A , A 2B and A 3 ligands 3 by employing advanced synthetic methodologies. In this talk, I will introduce our multicomponent-assisted platform for drug discovery using A 2B and A 3 receptors as case studies. The presentation will cover ligand discovery and optimization as well as preliminary evidences of the anticancer effect of some optimized ligands. References: [1] Fredholm, B. B.; Ijzerman, A. P.; Jacobson, K. A.; Linden, J.; Müller, C. E. Nomenclature and classification of adenosine receptors − An update. Pharmacol. Rev . 2011 , 63 , 1 −334. [2] Müller, C. E.; Jacobson, A. J. Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim. Biophys. Acta, 2011 , 1808 , 1290 −1308. [3] Crespo, A. El Maatougui, A. Biagini, P. Azuaje, J. Coelho, A. Brea, J. Loza, M. I. Cadavid, M. I. García-Mera, X. Gutiérrez-de-Terán, H. Sotelo, E. ACS Med. Chem. Lett . 2013 , 4 , 1031– 1036. El Maatougui, A., Azuaje, J., González-Gómez, M., Miguez, G., Crespo, A., Carbajales, C, Escalante, L., Gutiérrez de Terán, H., Sotelo, E., J. Med. Chem ., 2016 , 59 , 1967-1983. Carbajales, C., Azuaje, J., Oliveira, A., Loza, M. I., Brea, J., Cadavid, M.I., Masaguer, C.F., García-Mera, X., Gutiérrez de Terán, H., Sotelo, E., J. Med. Chem., 2017 , 60 , 3372-3382. Jespers, W. Scheidel, A.C., Heitman, L.H, Cooke, R.M., Kleene, L., van Westen, G.J., Gloriam, D.E., Müller, C.E, Sotelo, E., Gutiérrez de Terán, H., Trends Pharmacol. Sci ., 2018 , 39 , 75 −89.