Lin Xiao, Chai Ling, Liu Buming, Chen Hailan, Zheng Li, Liu Qin, Lin Cuiwu
School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530005, China.
Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China.
Molecules. 2016 Dec 23;22(1):3. doi: 10.3390/molecules22010003.
Gallic acid (GA) and its derivatives are anti-inflammatory agents and are reported to have potent effects on Osteoarthritis (OA) treatment. Nonetheless, it is generally accepted that the therapeutic effect and biocompatibility of GA is much weaker than its esters due to the high hydrophilicity. The therapeutic effect of GA on OA could be improved if certain structural modifications were made to increase its hydrophobicity. In this study, a novel sulfonamido-based gallate was synthesized by bonding sulfonamide with GA, and its biological evaluations on OA were investigated. Results show that 5-[4-(Pyrimidin-2-ylsulfamoylphenyl)]-carbamoyl-benzene-1,2,3-triyl triacetate (HAMDC) was able to reverse the effects induced by Interleukin-1 (IL-1) stimulation, and it also had a great effect on chondro-protection via promoting cell proliferation and maintaining the phenotype of articular chondrocytes, as well as enhancing synthesis of cartilage specific markers such as aggrecan, collagen II and Sox9. Furthermore, a docking study showed that HAMDC fits into the core of the active site of a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), which provides an explanation for its activity and selectivity.
没食子酸（GA）及其衍生物是抗炎剂，据报道对骨关节炎（OA）治疗有显著效果。然而，由于高亲水性，GA的治疗效果和生物相容性通常被认为比其酯类弱得多。如果进行某些结构修饰以增加其疏水性，GA对OA的治疗效果可能会得到改善。在本研究中，通过将磺酰胺与GA结合合成了一种新型的基于磺酰胺的没食子酸酯，并对其对OA的生物学评价进行了研究。结果表明，5-[4-(嘧啶-2-基磺酰氨基苯基)]-氨基甲酰基苯-1,2,3-三基三乙酸酯（HAMDC）能够逆转白细胞介素-1（IL-1）刺激所诱导的效应，并且它还通过促进细胞增殖和维持关节软骨细胞的表型，以及增强软骨特异性标志物如聚集蛋白聚糖、胶原蛋白II和Sox9的合成，对软骨保护有很大作用。此外，一项对接研究表明，HAMDC适合结合到含血小板反应蛋白基序的解聚素和金属蛋白酶5（ADAMTS-5）活性位点的核心，这为其活性和选择性提供了解释。
