Abstract
The glyoxalase enzymes represent a cellular defence system against the accumulation of cytotoxic α-oxoaldehydes leading to apoptosis. The potential of glyoxalase inhibitors to act as novel anti-cancer agents for drugresistant tumours that over-express glyoxalase is currently under investigation. In the present study, a series of 6-sulfamoylsaccharin and 1,2-benzoxathiine 2,2-dioxide (sulfocoumarin - coumarin bioisostere) derivates, as well as, transcinnamic acid (the mimic of coumarin hydrolysis product) have been tested for the inhibition of glyoxalase 1 and 2. For the first time, it has been demonstrated, that 6-sulfamoylsaccharin possesses glyoxalase 1 inhibitory activity (IC50=90±15 μM). Two compounds, 5b and 9c, slightly inhibited the activity of glyoxalase 2. In addition, it has been demonstrated that trans-cinnamic acid inhibits glyoxalase 1 activity (IC 50=84±4 μM). These data indicate that the modification of 6-sulfamoylsaccharin structure and coumarin hydrolysis products can be used to develop potential glyoxalase 1 inhibitors.
| Original language | English |
|---|---|
| Pages (from-to) | 410-414 |
| Number of pages | 5 |
| Journal | Letters in Drug Design and Discovery |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jun 2013 |
Keywords*
- 1,2-benzoxathiine 2,2-dioxide
- 6-sulfamoylsaccharin
- Glyoxalase 1
- Glyoxalase 2
- Sulfocoumarin
- Trans-cinnamic acid
Field of Science*
- 1.6 Biological sciences
- 3.1 Basic medicine
Publication Type*
- 1.1. Scientific article indexed in Web of Science and/or Scopus database
