Identification of new non-carboxylic acid containing inhibitors of aldose reductase

Rosanna Maccari, Rosella Ciurleo, Marco Giglio, Mario Cappiello, Roberta Moschini, Antonella Del Corso, Umberto Mura, Rosaria Ottanà

Research output: Contribution to journalArticlepeer-review


Non-carboxylic acid containing bioisosteres of (5-arylidene-2,4-dioxothiazolidin-3-yl)acetic acids, which are active as aldose reductase (ALR2) inhibitors, were designed by replacing the carboxylic group with the trifluoromethyl ketone moiety. The in vitro evaluation of the ALR2 inhibitory effects of these trifluoromethyl substituted derivatives led to the identification of two inhibitors effective at low micromolar doses. It was further confirmed that a carboxylic chain on N-3 of the thiazolidinedione scaffold is a determining requisite to obtain the highest efficacy levels; however, it is not essential for the interaction with the target enzyme and it can be replaced by different polar groups, thus obtaining less ionised or unionised inhibitors.

Original languageEnglish
Pages (from-to)4049-4055
Number of pages7
JournalBioorganic and Medicinal Chemistry
Issue number11
Publication statusPublished - Jun 1 2010


  • 2,4-Thiazolidinediones
  • Aldose reductase inhibitors
  • Diabetes complications
  • In vitro inhibition

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science


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