Discovery of novel 1, 3, 5‐triazine as adenosine A2A receptor antagonist for benefit in Parkinson's disease. Issue 3 (6th November 2020)

• Record Type: Journal Article
• Authors: Masih, Anup; Agnihotri, Amol K.; Srivastava, Jitendra K.; Pandey, Nidhi; Bhat, Hans R.; Singh, Udaya P.
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 35:Issue 3(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-06
• Subjects: adenosine A2A receptor -- antagonist -- 1, 3, 5‐triazine -- docking -- Parkinson's disease; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.22659
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: 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 A2 A receptor (A2 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 A2 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 A2 AR cDNA and pcDNA 3.1(+) containing full‐length human A1 R cDNA, where they exhibit selective affinity for A2 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 A2 AR. It has been shown that compound 7c form numerous nonbonded interactions in the active site of A2 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 A2 AR antagonists.