کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5823646 1118346 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Different efficacy of adenosine and NECA derivatives at the human A3 adenosine receptor: Insight into the receptor activation switch
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Different efficacy of adenosine and NECA derivatives at the human A3 adenosine receptor: Insight into the receptor activation switch
چکیده انگلیسی

A3 Adenosine receptors are promising drug targets for a number of diseases and intense efforts are dedicated to develop selective agonists and antagonists of these receptors. A series of adenosine derivatives with 2-(ar)-alkynyl chains, with high affinity and different degrees of selectivity for human A3 adenosine receptors was tested for the ability to inhibit forskolin-stimulated adenylyl cyclase. All these derivatives are partial agonists at A3 adenosine receptors; their efficacy is not significantly modified by the introduction of small alkyl substituents in the N6-position. In contrast, the adenosine-5′-N-ethyluronamide (NECA) analogs of 2-(ar)-alkynyladenosine derivatives are full A3 agonists. Molecular modeling analyses were performed considering both the conformational behavior of the ligands and the impact of 2- and 5′-substituents on ligand-target interaction. The results suggest an explanation for the different agonistic behavior of adenosine and NECA derivatives, respectively. A sub-pocket of the binding site was analyzed as a crucial interaction domain for receptor activation.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 87, Issue 2, 15 January 2014, Pages 321-331
نویسندگان
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