Correlation study between A 3 adenosine receptor binding affinity and anti-renal interstitial fibrosis activity of truncated adenosine derivatives.

Truncated 4'-thionucleosides 1-4 and 4'-oxonucleosides 5-8 as potent and selective A3 AR 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 A3 AR were proportional to their inhibitory activities against TGF-β1-induced collagen I upregulation in mProx cells. This result suggests that the binding affinity of A3 AR antagonists is closely correlated with their anti-fibrotic activity. Thus, A3 AR antagonists might be novel therapeutic candidates for treating chronic kidney disease.