Discovery of novel 1,3,5-triazine as adenosine A2A receptor antagonist for benefit in Parkinson's disease

Parkinson's disease (PD) is a chronic neuro-degenerative ailment characterized by impairment in various motor and nonmotor functions of the body. In the past few years, adenosine A(2)A receptor (A(2)AR) antagonists have attracted much attention due to significant relief in PD. Therefore, in the current study, we intend to disclose the development of novel 1,3,5-triazines as A(2)AR antagonist. The radioligand binding and selectivity of analogs were tested in HEK293 (human embryonic kidney) and the cells were transfected with pcDNA 3.1(+) containing full-length human A(2)AR cDNA and pcDNA 3.1(+) containing full-length human A(1)R cDNA, where they exhibit selective affinity for A(2)AR. Molecular docking analysis was also conducted to rationalize the probable mode of action, binding affinity, and orientation of the most potent molecule (7c) at the active site of A(2)AR. It has been shown that compound 7c form numerous nonbonded interactions in the active site of A(2)AR by interacting with Ala59, Ala63, Ile80, Val84 Glu169, Phe168, Met270, and Ile274. The study revealed 1,3,5-triazines as a novel class of A(2)AR antagonists.

Automated summary

Parkinson's disease is characterized by motor and nonmotor impairments, and there is growing interest in adenosine A(2)A receptor antagonists for relief in PD. In this study, novel 1,3,5-triazines were developed and shown to act as A(2)AR antagonists through cell testing and molecular docking analysis, exhibiting promising potential for treatment.