Correlation study between A3 adenosine receptor binding affinity and anti-renal interstitial fibrosis activity of truncated adenosine derivatives

Arch Pharm Res. 2019 Sep;42(9):773-779. doi: 10.1007/s12272-018-1079-2. Epub 2018 Sep 27.

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.

Keywords: A3 adenosine receptor; Antagonist; Binding affinity; Renal fibrosis; Truncated adenosine.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / chemistry
  • Adenosine / pharmacology*
  • Adenosine A3 Receptor Antagonists / chemical synthesis
  • Adenosine A3 Receptor Antagonists / chemistry
  • Adenosine A3 Receptor Antagonists / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Fibrosis / drug therapy*
  • Fibrosis / metabolism
  • Humans
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / metabolism
  • Molecular Structure
  • Rats
  • Receptor, Adenosine A3 / metabolism*
  • Structure-Activity Relationship

Substances

  • Adenosine A3 Receptor Antagonists
  • Receptor, Adenosine A3
  • Adenosine