Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry


Docking‘s study of 6-substituted adenosine-5'-n-ethyluronamide analogs as selective agonists at a3 adenosine receptor and selection of compounds for to be synthesized later

Author(s): Francisco Valdés Z., Víctor Luna Z., Bárbara Arévalo R., Nelson Brown V. and Margarita Gutiérrez C.

Adenosine is an endogenous nucleoside distributed throughout the body and is recognized electrophysiological effects since 1929. For its part, adenosine analogs and conjugates are of great importance and have multiple applications as drugs for cardiovascular, immune therapy and other diseases. In addition, the receptors that interact with adenosine and its derivatives are purinergic type, classified as A1, A2A, A2B and A3, which together in the presence of agonists and antagonists are involved in various diseases or diseases affecting the normal operation body. Thus, the aim of this research was to perform a study of molecular coupling (docking) of adenosine–5'– ethyluronamide analogues with the A3 adenosine receptor, homology modeling previously. For this, a 3D model was obtained, in wichexperiments molecular docking were doneand selection filter of those molecular structures was made, showing those moleculeswith the best interactions and contacts with the amino acid residues of interest given in the active-site of such receiver. Of a total 417 poses was obtained by 35 molecules of adenosine - 5 '- ethyluronamide analogues were designed in silico214 poses were obtained and produced interactions with all residues of interestcorresponding to 21 compounds including to selective agonists such as IB-MECA and nonselective agonist NECA. Furthermore, the poses of the 21 compounds were selected according to two criteria: binding energy shown; and interactions with the amino acid residues of the active-site of the A3 receptor. Finally, according to statistics data, were selected the poses of the top 9 compounds showed lower binding energies and very close values of the selective agonist (IB-MECA) and were founded below average calculated(-54.98 Kcal/mol), with exception of NECA because it showed a high binding energy compared to the average.Finally, the selected compounds showed statistically significant differences, which it allows geta pool of candidate molecules for to be synthesized in order to act as selective ligands on A3 receptor, who could be used as a promising therapeutic target in anti-tumor activity reported in various cell lines.