1. Correlation study between A 3 adenosine receptor binding affinity and anti-renal interstitial fibrosis activity of truncated adenosine derivatives.
- Author
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Yu J, Kim G, Jarhad DB, Lee HW, Lee J, Park CW, Ha H, and Jeong LS
- Subjects
- Adenosine analogs & derivatives, Adenosine chemistry, Adenosine A3 Receptor Antagonists chemical synthesis, Adenosine A3 Receptor Antagonists chemistry, Animals, Dose-Response Relationship, Drug, Fibrosis metabolism, Humans, Kidney Diseases metabolism, Molecular Structure, Rats, Structure-Activity Relationship, Adenosine pharmacology, Adenosine A3 Receptor Antagonists pharmacology, Fibrosis drug therapy, Kidney Diseases drug therapy, Receptor, Adenosine A3 metabolism
- 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 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.- Published
- 2019
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