title: Heteroarylimino-4-thiazolidinones as inhibitors of cartilage degradation.
abstract: 2-Benzo[d]thiazolyl- and 2-benzo[d]isothiazolyl-imino-5-benzylidene-4-thiazolidinone derivatives were investigated as potential metalloproteinases (MMPs) inhibitors and evaluated for their antidegenerative activity on human chondrocyte cultures stimulated by IL-1β, using an experimental model that reproduces the mechanisms involved in osteoarthritic (OA) diseases. Cell viability, the amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) were measured. The most potent compound, 5-(4-methoxy-benzylidene)-2-(benzo[d]isothiazol-3-ylimino)-thiazolidin-4-one (4b), a MMP-13 inhibitor at nanomolar concentration (IC(50)=0.036 μM), could be considered as a lead compound for the development of novel clinical agents, inhibitors of cartilage degradation, for the treatment of OA.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Catania, Viale A. Doria 6, Catania, Italy. panico@unict.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Panico
authors.forename: Paola
authors.initials: P
authors.lastname: Vicini
authors.forename: Athina
authors.initials: A
authors.lastname: Geronikaki
authors.forename: Matteo
authors.initials: M
authors.lastname: Incerti
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
authors.forename: Lucia
authors.initials: L
authors.lastname: Crascì
authors.forename: Rossella
authors.initials: R
authors.lastname: Messina
authors.forename: Simone
authors.initials: S
authors.lastname: Ronsisvalle
mesh_terms: D002356:Cartilage / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D045726:Metalloproteases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009589:Nitrogen Oxides / Q000276:immunology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D053778:Thiazolidines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D009589:Nitrogen Oxides; D053778:Thiazolidines; D045726:Metalloproteases