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

Jinha Yu; Gyudong Kim; Dnyandev B. Jarhad; Hyuk Woo Lee; Jiyoun Lee; Chong Woo Park; Hunjoo Ha; Lak Shin Jeong

doi:10.1007/s12272-018-1079-2

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

Jinha Yu, Gyudong Kim, Dnyandev B. Jarhad, Hyuk Woo Lee, Jiyoun Lee, Chong Woo Park, Hunjoo Ha, Lak Shin Jeong

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English
Pages (from-to)	773-779
Number of pages	7
Journal	Archives of Pharmacal Research
Volume	42
Issue number	9
DOIs	https://doi.org/10.1007/s12272-018-1079-2
State	Published - 1 Sep 2019

Bibliographical note

Publisher Copyright:
© 2018, The Pharmaceutical Society of Korea.

Keywords

A adenosine receptor
Antagonist
Binding affinity
Renal fibrosis
Truncated adenosine

Access to Document

10.1007/s12272-018-1079-2

Cite this

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title = "Correlation study between A3 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 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 = "A adenosine receptor, Antagonist, Binding affinity, Renal fibrosis, Truncated adenosine",

author = "Jinha Yu and Gyudong Kim and Jarhad, {Dnyandev B.} and Lee, {Hyuk Woo} and Jiyoun Lee and Park, {Chong Woo} and Hunjoo Ha and Jeong, {Lak Shin}",

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AU - Yu, Jinha

AU - Kim, Gyudong

AU - Jarhad, Dnyandev B.

AU - Lee, Hyuk Woo

AU - Lee, Jiyoun

AU - Park, Chong Woo

AU - Ha, Hunjoo

AU - Jeong, Lak Shin

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AB - 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.

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KW - Antagonist

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KW - Truncated adenosine

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