Identification of 5-arylidene-4-thiazolidinone derivatives endowed with dual activity as aldose reductase inhibitors and antioxidant agents for the treatment of diabetic complications

In continuing the search for more effective 5-arylidene-4-thiazolidinones as aldose reductase inhibitors, a new set of suitably substituted compounds (4, 5 and 8) was explored. Acetic acids 5, particularly 5a and 5h, proved to be interesting inhibitors of the enzyme as well as excellent antioxidant agents that are potentially able to counteract the oxidative stress associated with both diabetic complications as well as other pathologies. Molecular docking experiments supported SAR studies.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 5-Arylidene-2,4-thiazolidinediones 4, 5 and 2-phenylimino analogues 8 inhibit ALR2. ► Compounds 5 reach ALR2 inhibitory activity levels similar to that of epalrestat. ► Compounds 5 are inhibitors more effective than sorbinil. ► 5a and 5h are endowed with dual activity as ALR2 inhibitors and antioxidant agents. ► Molecular modeling calculations allowed us to propose a hypothesis to explain SARs.