8-(Furan-2-yl)-3-phenethylthiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione as novel, selective and potent adenosine A(2A) receptor antagonist.

Abstract

Antagonism of the human A2A receptor has been implicated to alleviate the symptoms associated with Parkinson's disease. The present finding reveals the potential of PTTP (8-(furan-2-yl)-3-phenethylthiazolo[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione) as novel and potent A2AR antagonist. In radioligand binding assay, PTTP showed significantly high binding affinity (Ki 6.3 nM) and selectivity with A2AR (A1R/A2AR=4603) which was comparable to the results of docking analysis (Ki=1.6 nM, ΔG=-14.52 Kcal/mol). PTTP antagonized (0.46 pmol/ml) the effect of NECA-induced increase in cAMP concentration (0.65 pmol/ml) better than SCH58261 (0.55 pmol/ml) in HEK293T cells. Haloperidol and NECA-induced mice pre-treated with PTTP at 10mg/kg showed attenuation in catalepsy and akinesia without significant neurotoxicity in rotarod test at 20mg/kg. Essentially, novel compound demonstrated remarkable potential as A2AR antagonist in the therapy of PD.

• Authors: Namrata Kumari, Chandra Bhushan Mishra, Amresh Prakash, Nitin Kumar, Rajkumar Mongre, Pratibha Mehta Luthra
• Journal: Neuroscience letters (Neurosci Lett) Vol. 558 Pg. 203-7 (Jan 13 2014) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 24161891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 8-(furan-2-yl)-3-phenethylthiazolo(1,2,4)triazolo(1,5-c)pyrimidine-2(3H)-thione
• Adenosine A2 Receptor Antagonists
• Heterocyclic Compounds, 3-Ring
• Pyrimidines
• Receptor, Adenosine A2A
• Triazoles
• Cyclic AMP
• pyrimidine

Topics

• Adenosine A2 Receptor Antagonists (pharmacology)
• Animals
• Catalepsy (chemically induced, psychology)
• Cyclic AMP (metabolism)
• HEK293 Cells
• Heterocyclic Compounds, 3-Ring (pharmacology)
• Humans
• Male
• Mice
• Molecular Docking Simulation
• Motor Activity (drug effects)
• Pyrimidines (pharmacology)
• Radioligand Assay
• Receptor, Adenosine A2A (metabolism)
• Rotarod Performance Test
• Triazoles (pharmacology)