Effect of a novel synthesized sulfonamido-based gallate-SZNTC on chondrocytes metabolism in vitro

• Published in: Chemico-biological interactions Vol. 221; pp. 127 - 138
• Main Authors: Liu, Qin, Li, Mu-Yan, Lin, Xiao, Lin, Cui-Wu, Liu, Bu-Ming, Zheng, Li, Zhao, Jin-Min
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 25.09.2014
• Subjects: Benzamides - chemistry; Benzamides - pharmacology; Cell Proliferation; Cell Survival; Cells, Cultured; Chondro-protective effect; Chondrocytes - drug effects; Gallate acid; Gallic Acid - chemistry; Gallic Acid - pharmacology; Humans; Immunohistochemistry; Matrix Metalloproteinase 1 - metabolism; Modification; Osteoarthritis; Pharmacological effect; Polymerase Chain Reaction; Sulfathiazole sodium; Sulfathiazoles - chemistry; Sulfathiazoles - pharmacology; Sulfonamides - chemistry; Sulfonamides - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Gallate acid; Modification; Chondro-protective effect; Osteoarthritis; Sulfathiazole sodium; Pharmacological effect
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2014.08.002

•A novel compound SNZTC was synthesized from sulfathiazole sodium and gallic acid.•SZNTC was demonstrated ability to reduce the progression of osteoarthritis in vitro.•SZNTC can exert chondro-protective effects.•SZNTC showed better chondro-protective and pharmacological effects than its source.•SNZTC as a promising novel agent is promising in the treatment of osteoarthritis. The ideal therapeutic agent for treatment of osteoarthritis (OA) should have not only potent anti-inflammatory effect but also favorable biological properties to restore cartilage function. Gallic acid (GA) and its derivatives are anti-inflammatory agents reported to have an effect on OA (Singh et al., 2003) [1]. However, GA has much weaker antioxidant effects and inferior bioactivity compared with its derivatives. We modified GA with the introduction of sulfonamide to synthesize a novel sulfonamido-based gallate named sodium salt of 3,4,5-trihydroxy-N-[4-(thiazol-2-ylsulfamoyl)-phenyl]-benzamide (SZNTC) and analyzed its chondro-protective and pharmacological effects. Comparison of SZNTC with GA and sulfathiazole sodium (ST-Na) was also performed. Results showed that SZNTC could effectively inhibit the Interleukin-1 (IL-1)-mediated induction of metalloproteinase-1 (MMP-1) and MMP-3 and could induce the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), which demonstrated ability to reduce the progression of OA. SZNTC can also exert chondro-protective effects by promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as evidenced by improved cell growth, enhanced synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Expression of the collagen I gene was effectively down-regulated, revealing the inhibition of chondrocytes dedifferentiation by SZNTC. Hypertrophy that may lead to chondrocyte ossification was also undetectable in SZNTC groups. The recommended dose of SZNTC ranges from 3.91μg/ml to 15.64μg/ml, among which the most profound response was observed with 7.82μg/ml. In contrast, its source products of GA and ST-Na have a weak effect in the bioactivity of chondrocytes, which indicated the significance of this modification. This study revealed SZNTC as a promising novel agent in the treatment of chondral and osteochondral lesions.