Graduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, Brazil.
Laboratory of Modeling and Computational Chemistry, Department of Biological Sciences and Health, Federal University of Amapá, Macapá, Brazil.
J Biomol Struct Dyn. 2021 Jun;39(9):3115-3127. doi: 10.1080/07391102.2020.1761878. Epub 2020 May 6.
Adenosine A receptor (AR) is the predominant receptor in immune cells, where its activation triggers cAMP-mediated immunosuppressive signaling and the underlying inhibition of T cells activation and T cells-induced effects mediated by cAMP-dependent kinase proteins mechanisms. In this study, were used ADME/Tox, molecular docking and molecular dynamics simulations to investigate selective adenosine AR agonists as potential anti-inflammatory drugs. As a result, we obtained two promising compounds (A and B) that have satisfactory pharmacokinetic and toxicological properties and were able to interact with important residues of the AR binding cavity and during the molecular dynamics simulations were able to keep the enzyme complexed.Communicated by Ramaswamy H. Sarma.
腺苷 A 受体 (AR) 是免疫细胞中的主要受体，其激活触发 cAMP 介导的免疫抑制信号转导，以及 cAMP 依赖性激酶蛋白机制介导的 T 细胞激活和 T 细胞诱导效应的潜在抑制。在这项研究中，我们使用 ADME/Tox、分子对接和分子动力学模拟来研究选择性腺苷 AR 激动剂作为潜在的抗炎药物。结果，我们获得了两种有前途的化合物 (A 和 B)，它们具有令人满意的药代动力学和毒理学特性，能够与 AR 结合腔的重要残基相互作用，并且在分子动力学模拟过程中能够保持酶复合物的状态。由 Ramaswamy H. Sarma 传达。
