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

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5 Citations (Scopus)


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
Issue number3
Publication statusPublished - Mar 1 2016


ASJC Scopus subject areas

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

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