We report the synthesis, the antioxidant and the inhibitory activity (IC50) on metalloproteinases (MMPs)3 and 13 of 2-benzo[d]isothiazolylimino-5-benzylidene-4-thiazolidinones. Their potential as protectiveagents in osteoarthritis (OA) was evaluated by biological assays on chondrocytes cultures, stimulatedby IL-1b. The chondroprotective capability, related both to antioxidant activity and to inhibition of MMPs,was studied in vitro, by determining nitric oxide production and glycosaminoglycans release. Moreover,selected derivatives1hand1gwas studied for nuclear factor kappaB (NF-jB) inhibition by Western Blotanalysis and for MMP-3 protein release using ELISA test. The structure–activity relationship of testedcompounds demonstrates a favorable effect of theparasubstitution on the 5-benzilydene ring. Com-pound1gshows a potent and selective activity on MMP-3 versus MMP-13. Accordingly,1gpossesseshigh antioxidant effect, NO lowering and GAGs restoring capability and also reduces the production ofMMPs and NF-jB expression. Thus1gcan be considered as new potential chondroprotective agents

2-Benzisothiazolylimino-5benzylidene-4-thiazolidiones as protective agents against cartilage destruction

CARDILE, Venera;AVONDO, Sergio;PANICO, Anna Maria
2015

Abstract

We report the synthesis, the antioxidant and the inhibitory activity (IC50) on metalloproteinases (MMPs)3 and 13 of 2-benzo[d]isothiazolylimino-5-benzylidene-4-thiazolidinones. Their potential as protectiveagents in osteoarthritis (OA) was evaluated by biological assays on chondrocytes cultures, stimulatedby IL-1b. The chondroprotective capability, related both to antioxidant activity and to inhibition of MMPs,was studied in vitro, by determining nitric oxide production and glycosaminoglycans release. Moreover,selected derivatives1hand1gwas studied for nuclear factor kappaB (NF-jB) inhibition by Western Blotanalysis and for MMP-3 protein release using ELISA test. The structure–activity relationship of testedcompounds demonstrates a favorable effect of theparasubstitution on the 5-benzilydene ring. Com-pound1gshows a potent and selective activity on MMP-3 versus MMP-13. Accordingly,1gpossesseshigh antioxidant effect, NO lowering and GAGs restoring capability and also reduces the production ofMMPs and NF-jB expression. Thus1gcan be considered as new potential chondroprotective agents
Chondroprotective activity, Metalloproteinase-3, Metalloproteinase-13, ORAC, GlycosaminoglycansThiazolidinones
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/17094
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