Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin

International Journal of Molecular Sciences
Feng-Cheng LiuJenn-Haung Lai

Abstract

In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory flavonoid present in many different fruits and vegetables. We investigated the immunomodulatory effects of this compound, namely 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02), in a side-by-side comparison with quercetin. Chondrocytes were isolated from pig joints or the joints of patients with osteoarthritis that had undergone total knee replacement surgery. Several measures were used to assess the immunomodulatory potency of these compounds in tumor necrosis factor (TNF-α)-stimulated chondrocytes. Characterization included the protein and mRNA levels of molecules associated with arthritis pathogenesis as well as the inducible nitric oxide synthase (iNOS)⁻nitric oxide (NO) system and matrix metalloproteinases (MMPs) in cultured chondrocytes and proteoglycan, and aggrecan degradation in cartilage explants. We also examined the ac...Continue Reading

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Citations

Apr 17, 2019·International Journal of Molecular Sciences·Chih-Hsin Tang
Dec 30, 2020·The Journal of Pathology·Shin-Ruen YangAnn Chen
Jul 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shin-Ruen YangShuk-Man Ka

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Methods Mentioned

BETA
electrophoresis
X-ray

Software Mentioned

Alpha EaseFC

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