Molecular modeling approaches of selective adenosine receptor type 2A agonists as potential anti-inflammatory drugs

Abstract

Adenosine A_2A receptor (A_2AR) 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 A_2AR 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 A_2AR binding cavity and during the molecular dynamics simulations were able to keep the enzyme complexed.

Communicated by Ramaswamy H. Sarma

Keywords:

• New drugs
• anti-inflammatory compound
• A2AR selectivity
• molecular docking
• ADME/tox properties

Acknowledgements

We gratefully acknowledge the financial support provided by the FAPESP/USP (14/11009-1). The authors would like to thank the Graduate Program in Medicinal Chemistry and Molecular Modeling (UFPA-Brazil) from the Laboratory of Modeling and Computational Chemistry (LMCC) of Federal University of Amapá (UNIFAP-Brazil) and Brazilian Center for Physical Research of Rio de Janeiro-Brazil by computational support.

Disclosure statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.