Evaluation of the anti-inflammatory/chondroprotective activity of aldose reductase inhibitors in human chondrocyte cultures

Abstract

(5-Arylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic acids (6) and 5-arylidene-4-oxo-2-thioxothiazolidines (7), which we recently synthesised and assayed as aldose reductase inhibitors, were evaluated as anti-inflammatory/antidegenerative agents in cultures of human chondrocytes stimulated by IL-1β. In this screening, most of the tested compounds were able to control key components of the IL-1β-induced inflammatory signalling, by reducing the levels of NF-kB, ICAM-1, and NO as well as increasing the production of glycosaminoglycans by chondrocytes. Moreover, these 4-thiazolidinone derivatives exhibited antioxidant properties and were shown to inhibit MMP-3 and MMP-13 at micromolar concentrations, with a generally marked preference toward MMP-13 which plays a major role in cartilage degeneration. Thus, on the whole, compounds 6 and 7 were shown to be capable of both counteracting inflammatory events and contributing to restore normal levels of cartilage components. This anti-inflammatory/antidegenerative profile makes them interesting cell-permeable molecules that can be assumed as lead compounds in the search for novel anti-inflammatory agents.