dos Santos, Kelton L.B.Cruz, Jorddy N.Silva, Luciane B.Ramos, Ryan S.Neto, Moysés F.A.Lobato, Cleison C.Ota, Sirlene S.B.Leite, Franco H.A.Borges, Rosivaldo S.da Silva, Carlos H.T.P.Campos, Joaquín M.Santos, Cleydson B.R.2022-08-012022-08-012020-03-10Santos KLBD, Cruz JN, Silva LB, Ramos RS, Neto MFA, Lobato CC, et al. Identification of Novel Chemical Entities for Adenosine Receptor Type 2A Using Molecular Modeling Approaches. Molecules. 2020 Mar 10;25(5):1245http://hdl.handle.net/10668/3861Adenosine Receptor Type 2A (A2AAR) plays a role in important processes, such as anti-inflammatory ones. In this way, the present work aimed to search for compounds by pharmacophore-based virtual screening. The pharmacokinetic/toxicological profiles of the compounds, as well as a robust QSAR, predicted the binding modes via molecular docking. Finally, we used molecular dynamics to investigate the stability of interactions from ligand-A2AAR. For the search for A2AAR agonists, the UK-432097 and a set of 20 compounds available in the BindingDB database were studied. These compounds were used to generate pharmacophore models. Molecular properties were used for construction of the QSAR model by multiple linear regression for the prediction of biological activity. The best pharmacophore model was used by searching for commercial compounds in databases and the resulting compounds from the pharmacophore-based virtual screening were applied to the QSAR. Two compounds had promising activity due to their satisfactory pharmacokinetic/toxicological profiles and predictions via QSAR (Diverset 10002403 pEC50 = 7.54407; ZINC04257548 pEC50 = 7.38310). Moreover, they had satisfactory docking and molecular dynamics results compared to those obtained for Regadenoson (Lexiscan®), used as the positive control. These compounds can be used in biological assays (in vitro and in vivo) in order to confirm the potential activity agonist to A2AAR.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Adenosine A2A receptorVirtual screeningMolecular insightAgonistas del receptor de adenosina A2Cribado sistemáticoSimulación del acoplamiento molecularRelación estructura-actividad cuantitativaSimulación de Dinámica MolecularMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Purines::Purine Nucleosides::AdenosineMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Purinergic Agents::Purinergic Agonists::Purinergic P1 Receptor Agonists::Adenosine A2 Receptor AgonistsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::LigandsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Docking SimulationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Molecular::Molecular Dynamics SimulationMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Structure-Activity Relationship::Quantitative Structure-Activity RelationshipMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Purinergic::Receptors, Purinergic P1::Receptors, Adenosine A2Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Purinergic::Receptors, Purinergic P1Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Statistical::Linear Modelsresearch article32164183Acceso abierto10.3390/molecules250512451420-3049PMC7179438