A New Application of Parallel Synthesis Strategy for Discovery of Amide-Linked Small Molecules as Potent Chondroprotective Agents in TNF-alpha-Stimulated Chondrocytes

作者：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

来源：PLos One, 2016, 11(3): e0149317.

DOI：10.1371/journal.pone.0149317

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-alpha)-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-alpha-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-kappa B) 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.

• 出版日期2016-3-10
• 单位长春大学; 河北医科大学