In vitro evaluation of 5-arylidene-2-thioxo-4-thiazolidinones active as aldose reductase inhibitors

Bioorg Med Chem Lett. 2011 Jan 1;21(1):200-3. doi: 10.1016/j.bmcl.2010.11.041. Epub 2010 Nov 12.

Abstract

2-Thioxo-4-thiazolidinone derivatives were evaluated as aldose reductase inhibitors (ARIs) and most of them exhibited good or excellent in vitro efficacy. Out of the tested compounds, most N-unsubstituted analogues were found to possess inhibitory effects at low micromolar doses and two of them exhibited higher potency than sorbinil, used as a reference drug. The insertion of an acetic chain on N-3 of the thiazolidinone scaffold led to analogues with submicromolar affinity for ALR2 and IC(50) values very similar to that of epalrestat, the only ARI currently used in therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Aldehyde Reductase / metabolism
  • Animals
  • Cattle
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Imidazolidines / chemistry
  • Imidazolidines / pharmacology
  • Structure-Activity Relationship
  • Thiazolidinediones / chemical synthesis
  • Thiazolidinediones / chemistry*
  • Thiazolidinediones / pharmacology

Substances

  • Enzyme Inhibitors
  • Imidazolidines
  • Thiazolidinediones
  • Aldehyde Reductase
  • sorbinil