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

5 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\}",

note = "Publisher Copyright: {\textcopyright} 2018, The Pharmaceutical Society of Korea.",

year = "2019",

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doi = "10.1007/s12272-018-1079-2",

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T1 - Correlation study between A3 adenosine receptor binding affinity and anti-renal interstitial fibrosis activity of truncated adenosine derivatives

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

PY - 2019/9/1

Y1 - 2019/9/1

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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.

KW - A adenosine receptor

KW - Antagonist

KW - Binding affinity

KW - Renal fibrosis

KW - Truncated adenosine

UR - https://www.scopus.com/pages/publications/85054181024

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