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

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• 作者：Namrata Kumari ; Ch ; ra Bhushan Mishra ; Amresh Prakash ; Nitin Kumar ; Rajkumar Mongre ; Pratibha Mehta Luthra
• 关键词：Adenosine A2A receptors (A2AR) ; cAMP ; Catalepsy ; Motor activity ; Mouse models of Parkinson ; PTTP
• 刊名：Neuroscience Letters
• 出版年：13 January, 2014
• 年：2014
• 卷：558
• 期：Complete
• 页码：203-207
• 全文大小：1159 K

文摘

Antagonism of the human A_2A 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 A_2AR antagonist. In radioligand binding assay, PTTP showed significantly high binding affinity (K_i 6.3 nM) and selectivity with A_2AR (A₁R/A_2AR = 4603) which was comparable to the results of docking analysis (K_i = 1.6 nM, 螖G = 鈭?4.52 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 HEK293 T cells. Haloperidol and NECA-induced mice pre-treated with PTTP at 10 mg/kg showed attenuation in catalepsy and akinesia without significant neurotoxicity in rotarod test at 20 mg/kg. Essentially, novel compound demonstrated remarkable potential as A_2AR antagonist in the therapy of PD.