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Correlation study between A3 adenosine receptor binding affinity and anti-renal interstitial fibrosis activity of
Jinha Yu1, Gyudong Kim1, Dnyandev B Jarhad1
1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.
Abstract:
Truncated 4'-thionucleosides 1-4 and 4'-oxonucleosides 5-8 as potent and selective A3AR antagonists were synthesized from D-mannose and D-erythronic acid γ-lactone, respectively. These nucleosides were evaluated for their anti-fibrotic renoprotective activity in TGF-β1-treated murine proximal tubular (mProx) cells. Their antagonistic activities for A3AR were proportional to their inhibitory activities against TGF-β1-induced collagen I upregulation in mProx cells. This result suggests that the binding affinity of A3AR antagonists is closely correlated with their anti-fibrotic activity. Thus, A3AR antagonists might be novel therapeutic candidates for treating chronic kidney disease.
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