In vitro effect of a synthesized sulfonamido-based gallate on articular chondrocyte metabolism

• Published in: Bioorganic & medicinal chemistry letters 2014-06, Vol.24 (11), p.2497-2503
• Main Authors: Lin, Xiao, Zheng, Li, Liu, Qin, Liu, Buming, Jiang, Bingli, Peng, Xiaoyu, Lin, Cuiwu
• Format: Article
• Language: English
• Subjects: Animals; Cartilage, Articular - cytology; Cartilage, Articular - drug effects; Cartilage, Articular - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Chondrocyte; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Dedifferentiation; Dose-Response Relationship, Drug; Gallic acid; Gallic Acid - analogs & derivatives; Gallic Acid - chemical synthesis; Gallic Acid - chemistry; Gallic Acid - pharmacology; Molecular Structure; Pro-chondrogenic agent; Rabbit articular cartilage; Rabbits; Structure-Activity Relationship; Sulfadimidine; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2014.04.015

Autologous chondrocyte implantation (ACI) is a promising strategy for cartilage repair and reconstitution. However, limited cell numbers and the dedifferentiation of chondrocytes present major difficulties to the success of ACI therapy. Therefore, it is important to find effective pro-chondrogenic agents that restore these defects to ensure a successful therapy. In this study, we synthesized a sulfonamido-based gallate, namely N-[4-(4,6-dimethyl-pyrimidin-2-ylsulfamoyl)-phenyl]-3,4,5-trihydroxy-benzamide (EJTC), and investigated its effects on rabbit articular chondrocytes through an examination of its specific effects on cell proliferation, morphology, viability, GAG synthesis, and cartilage-specific gene expression. The results show that EJTC can effectively promote chondrocyte growth and enhance the secretion and synthesis of cartilage ECM by upregulating the expression levels of the aggrecan, collagen II, and Sox9 genes. The expression of the collagen I gene was effectively downregulated, which indicates that EJTC inhibits chondrocytes dedifferentiation. Chondrocyte hypertrophy, which may lead to chondrocyte ossification, was also undetectable in the EJTC-treated groups. The recommended dose of EJTC ranges from 3.125μg/mL to 7.8125μg/mL, and the most profound response was observed with 7.8125μg/mL. This study may provide a basis for the development of a novel agent for the treatment of articular cartilage defects.