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Discovery of novel 1,3,5‐triazine as adenosine A 2A receptor antagonist for benefit in Parkinson's disease
Author(s) -
Masih Anup,
Agnihotri Amol K.,
Srivastava Jitendra K.,
Pandey Nidhi,
Bhat Hans R.,
Singh Udaya P.
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22659
Subject(s) - antagonist , docking (animal) , chemistry , receptor , binding site , adenosine receptor , stereochemistry , hek 293 cells , adenosine , complementary dna , pharmacology , biology , biochemistry , medicine , gene , agonist , nursing
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.