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Design and development of 1,3,5-triazine-thiadiazole hybrids as potent adenosine A 2 A receptor (A 2 AR) antagonist for benefit in Parkinson's disease.
- Source :
-
Neuroscience letters [Neurosci Lett] 2020 Sep 14; Vol. 735, pp. 135222. Date of Electronic Publication: 2020 Jun 30. - Publication Year :
- 2020
-
Abstract
- Various studies showed adenosine A <subscript>2</subscript> A receptors (A <subscript>2</subscript> ARs) antagonists have profound therapeutic efficacy in Parkinsons Disease (PD) by improving dopamine transmission, thus being active in reversing motor deficits and extrapyramidal symptoms related to the disease. Therefore, in the presents study, we have showed the development of novel 1,3,5-triazine-thiadiazole derivative as potent A <subscript>2</subscript> ARs antagonist. In the radioligand binding assay, these molecules showed excellent binding affinity with A <subscript>2</subscript> AR compared to A <subscript>1</subscript> R, with significant selectivity. Results suggest, compound 7e as most potent antagonist of A <subscript>2</subscript> AR among the tested series. In docking analysis with A <subscript>2</subscript> AR protein model, compound 7e found to be deeply buried into the cavity of receptor lined via making numerous interatomic contacts with His264, Tyr271, His278, Glu169, Ala63, Val84, Ile274, Met270, Phe169. Collectively, our study demonstrated 1,3,5-triazine-thiadiazole hybrid as a highly effective scaffold for the design of new A <subscript>2</subscript> A antagonists.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Adenosine A2 Receptor Antagonists metabolism
Adenosine A2 Receptor Antagonists therapeutic use
Antiparkinson Agents metabolism
Antiparkinson Agents therapeutic use
Crystallography, X-Ray methods
HEK293 Cells
Humans
Molecular Docking Simulation methods
Parkinson Disease drug therapy
Parkinson Disease metabolism
Protein Structure, Secondary
Radioligand Assay methods
Receptor, Adenosine A2A chemistry
Receptor, Adenosine A2A metabolism
Thiadiazoles metabolism
Thiadiazoles therapeutic use
Triazines metabolism
Triazines therapeutic use
Adenosine A2 Receptor Antagonists chemistry
Antiparkinson Agents chemistry
Drug Design
Drug Development methods
Thiadiazoles chemistry
Triazines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7972
- Volume :
- 735
- Database :
- MEDLINE
- Journal :
- Neuroscience letters
- Publication Type :
- Academic Journal
- Accession number :
- 32619652
- Full Text :
- https://doi.org/10.1016/j.neulet.2020.135222