Issue 5, 2015

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.

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

Article information

Article type
Concise Article
Submitted
12 Dec 2014
Accepted
01 Feb 2015
First published
04 Feb 2015

Med. Chem. Commun., 2015,6, 823-830

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

A. Panico, R. Maccari, V. Cardile, S. Avondo, L. Crascì and R. Ottanà, Med. Chem. Commun., 2015, 6, 823 DOI: 10.1039/C4MD00556B

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