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

Abstract

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 gamma-lactone, respectively. These nucleosides were evaluated for their anti-fibrotic renoprotective activity in TGF-beta 1-treated murine proximal tubular (mProx) cells. Their antagonistic activities for A(3)AR were proportional to their inhibitory activities against TGF-beta 1-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.