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 (IC₅₀=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.

Keywords: 1, 2-benzoxathiine 2, 2-dioxide, Glyoxalase 1, Glyoxalase 2, 6-sulfamoylsaccharin, Sulfocoumarin, Trans-cinnamic acid