期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 18, 期 7, 页码 2491-2500出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.02.048
关键词
A(2A)R; Antagonist; cAMP assay; Haloperidol; Radioligand-binding assay; Thiazolotriazolopyrimidines
资金
- Department of Science and Technology, Delhi,
- Department of Biotechnology, Delhi
- University Grant Commission, Delhi, India
- Council of Scientific and Industrial Research, Delhi, India
Novel thiazolotriazolopyrimidine derivatives (23-33) designed as potential adenosine A(2A) receptor (A(2A)R) antagonists were synthesized. Molecular docking studies revealed that all compounds (23-33) exhibited strong interaction with A(2A)R. The strong interaction of the compounds (23-33) with A(2A)R in silico was confirmed by their high binding affinity with human A(2A)R stably expressed in HEK293 cells using radioligand-binding assay. The compounds 24-26 demonstrated substantial binding affinity and selectivity for A(2A)R as compared to SCH58261, a standard A(2A)R antagonist. Decrease in A(2A)R-coupled release of endogenous cAMP in treated HEK293 cells demonstrated in vitro A(2A)R antagonist potential of the compounds 24-26. Attenuation in haloperidol-induced motor impairments (catalepsy and akinesia) in Swiss albino male mice pre-treated with compounds 24-26 further supports their role in the alleviation of PD symptoms. (C) 2010 Elsevier Ltd. All rights reserved.
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