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 A 3 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 A 3 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 A 3 AR antagonists is closely correlated with their anti-fibrotic activity. Thus, A 3 AR antagonists might be novel therapeutic candidates for treating chronic kidney disease.