title: Synthesis, Biological Evaluation, and Docking Studies of a Novel Sulfonamido-Based Gallate as Pro-Chondrogenic Agent for the Treatment of Cartilage.
abstract: 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.
authors.affiliation: School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530005, China. linxiaolegend@163.com.|Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China. linxiaolegend@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.affiliation: Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China. cicichai001@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Chai
authors.affiliation: Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China. liu_buming@163.com.
authors.forename: Buming
authors.initials: B
authors.lastname: Liu
authors.affiliation: Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Traditional Medical and Pharmaceutical Sciences, Nanning 530022, China. hlchen319@163.com.
authors.forename: Hailan
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China. zhengli224@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: The Medical and Scientific Research Center, Guangxi Medical University, Nanning 530021, China. liuqin_2001@163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530005, China. cuiwulin@163.com.
authors.forename: Cuiwu
authors.initials: C
authors.lastname: Lin
mesh_terms: D000071116:ADAMTS5 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020219:Chondrogenesis / Q000187:drug effects; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D053583:Interleukin-1beta / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D010003:Osteoarthritis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D061251:Primary Cell Culture; D011817:Rabbits; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C000616954:5-(4-(pyrimidin-2-ylsulfamoylphenyl)carbamoylbenzene-1,2,3-triyl triacetate; D053674:Aggrecans; D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D055758:SOX9 Transcription Factor; D013449:Sulfonamides; D019715:Tissue Inhibitor of Metalloproteinase-1; D005707:Gallic Acid; D000071116:ADAMTS5 Protein; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1
keywords: gallic acid; molecular docking; pro-chondrogenic agent; sulfadiazine sodium