Aspartic
proteases play very important role in post translational processing of
proteins and several of them are essential for organism's viability. Here we present the
enzyme inhibition activities of different Sulfamoylbenzamide derivatives against two aspartic
proteases cathepsin D and
plasmepsin II.
Cathepsin D is an aspartic
protease that degrades
proteins at acidic pH in the lysosomes, or extracellular matrix. It is overexpressed by epithelial
breast cancer cells and hence hyper-secreted. On the other hand
plasmepsin II is an essential
enzyme of Plasmodium falciperum.
Cathepsin D and
Plasmepsin II are pivotal
drug targets for treatment of
breast cancer and
malaria respectively. Virtual screening of Sulfamoylbenzamide compounds followed by
enzyme inhibition assays revealed these compounds as selective
Cathepsin D inhibitors while inactive against
Plasmepsin-II. IC50 values of five Sulfamoylbenzamide compounds tested are in range of 1.25-2.0 μM. N-(3-chlorophenyl)-2-sulfamoylbenzamide is identified as the most potent of all tested Sulfamoylbenzamide compounds with IC50 1.25 μM. It was also noted that the docking score of theses compounds was better in case of
Cathepsin D as compared to
Plasmepsin-II. Docking score ranges from -29.9±1.16 to -35.1±0.13 in case of
Cathepsin D, while from -24.0±0.10 to -29.5±0.10 in case of
Plasmepsin-II.