A new application of parallel synthesis strategy for discovery of amide-linked small molecules as potent chondroprotective agents in TNF-α-stimulated chondrocytes

Chia Chung Lee, Yang Lo, Ling Jun Ho, Jenn Haung Lai, Shiu Bii Lien, Leou Chyr Lin, Chun Liang Chen, Tsung Chih Chen, Feng Cheng Liu, Hsu Shan Huang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

As part of an effort to profile potential therapeutics for the treatment of inflammation-related diseases, a diversity of amide-linked small molecules was synthesized by using parallel synthesis strategy. Moreover, these new compounds were also evaluated for their inhibitory effects on nitric oxide (NO) by using tumor necrosis factor alpha (TNF-α)-induced inflammatory responses in chondrocytes. Among the tested compounds, N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide (HS-Ck) was the most potent inhibitor of NO production and inducible nitric oxide synthase (iNOS) expression in TNF-α-stimulated chondrocytes. In addition, our biological results indicated that HS-Ck might suppress the expression levels of iNOS and matrix metalloproteinases-13 (MMP-13) activities through downregulating the activation of nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT-3) transcriptional factors. Therefore, the parallel synthesis was successful used to develop a new class of potential anti-inflammatory agents as chondroprotective candidates for the treatment of osteoarthritis.

Original languageEnglish
Article numbere0149317
JournalPLoS One
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

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chondrocytes
Nitric Oxide Synthase Type II
Chondrocytes
amides
Amides
tumor necrosis factor-alpha
nitric oxide
Nitric Oxide
Tumor Necrosis Factor-alpha
inflammation
Matrix Metalloproteinase 13
anti-inflammatory agents
STAT3 Transcription Factor
Molecules
synthesis
NF-kappa B
osteoarthritis
Osteoarthritis
Anti-Inflammatory Agents
Down-Regulation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

A new application of parallel synthesis strategy for discovery of amide-linked small molecules as potent chondroprotective agents in TNF-α-stimulated chondrocytes. / Lee, Chia Chung; Lo, Yang; Ho, Ling Jun; Lai, Jenn Haung; Lien, Shiu Bii; Lin, Leou Chyr; Chen, Chun Liang; Chen, Tsung Chih; Liu, Feng Cheng; Huang, Hsu Shan.

In: PLoS One, Vol. 11, No. 3, e0149317, 01.03.2016.

Research output: Contribution to journalArticle

Lee, Chia Chung ; Lo, Yang ; Ho, Ling Jun ; Lai, Jenn Haung ; Lien, Shiu Bii ; Lin, Leou Chyr ; Chen, Chun Liang ; Chen, Tsung Chih ; Liu, Feng Cheng ; Huang, Hsu Shan. / A new application of parallel synthesis strategy for discovery of amide-linked small molecules as potent chondroprotective agents in TNF-α-stimulated chondrocytes. In: PLoS One. 2016 ; Vol. 11, No. 3.
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