Some sulfonamides as aldose reductase inhibitors: therapeutic approach in diabetes

Arch Physiol Biochem. 2022 Aug;128(4):979-984. doi: 10.1080/13813455.2020.1742166. Epub 2020 Mar 23.

Abstract

In this study, aldose reductase (AR) was purified from sheep kidney using chromatographic methods and examined the interactions between some sulfonamides and the enzyme. According to results, sulfonamides display effective inhibitor features for sheep kidney AR with IC50 values in the range of 37.27-87.65 μM and Kis in the range of 25.72 ± 6.45 to 73.56 ± 17.49 μM. The sulfonamides displayed different inhibition mechanisms. It was found that studied all compounds displayed non-competitive inhibition type except for 5-chlorothiophene-2-sulfonamide (1). It showed competitive inhibition. Among these compounds, 2,5-dichlorothiophene-3-sulfonamide compound (2) was showed the most potent AR inhibitor (Ki: 25.72 ± 6.45). These compounds may be useful in the treatment of diabetic complications.

Keywords: Enzyme purification; aldose reductase; enzyme inhibition; oxidative stress; sulfonamides.

MeSH terms

  • Aldehyde Reductase*
  • Animals
  • Diabetes Mellitus* / drug therapy
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Kidney
  • Sheep
  • Sulfonamides* / pharmacology

Substances

  • Enzyme Inhibitors
  • Sulfonamides
  • Aldehyde Reductase