A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-α-Stimulated Chondrocytes
作者： Chia-Chung Lee , Yang Lo , Ling-Jun Ho , Jenn-Haung Lai , Shiu-Bii Lien
DOI: 10.1371/JOURNAL.PONE.0149317
关键词: Chemistry 、 Nitric oxide 、 NFKB1 、 Immunology 、 Nitric oxide synthase 、 Small molecule 、 Transcription factor 、 Cell biology 、 STAT3 Transcription Factor 、 Tumor necrosis factor alpha 、 STAT protein
摘要: As part of an effort to profile potential therapeutics for the treatment inflammation-related diseases, a diversity amide-linked small molecules was synthesized by using parallel synthesis strategy. Moreover, these new compounds were also evaluated their inhibitory effects on nitric oxide (NO) tumor necrosis factor alpha (TNF-α)-induced inflammatory responses in chondrocytes. Among tested compounds, N-(3-chloro-4-fluorophenyl)-2-hydroxybenzamide (HS-Ck) most potent inhibitor NO production and inducible synthase (iNOS) expression TNF-α-stimulated In addition, our biological results indicated that HS-Ck might suppress levels iNOS matrix metalloproteinases-13 (MMP-13) activities through downregulating activation nuclear kappa B (NF-κB) signal transducer activator transcription 3 (STAT-3) transcriptional factors. Therefore, successful used develop class anti-inflammatory agents as chondroprotective candidates osteoarthritis.
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