Synthesis and biological evaluation of sulfamate derivatives as inhibitors of carbonic anhydrases II and IX

Inhibition of carbonic anhydrases is a potential avenue for treatment of various pathological conditions such as cancer, glaucoma, epileptic seizures, obesity, and altitude sickness. In this study, a series of 4-benzamidophenyl sulfamate derivatives were synthesized and tested against two carbonic anhydrase isoforms namely, carbonic anhydrase II (CA II) and carbonic anhydrase IX (CA IX). All the synthesized compounds inhibited the activity of both isoforms CA II and CA IX at micromolar IC50 concentrations. Compound 1n was found to be the most potent against CA II with an IC50 value of 0.78 mu M, whereas compound 1f was the most potent inhibitor against CA IX with an IC50 value of 0.34 mu M. Molecular modeling studies of the most potent compounds revealed a network of interactions with important amino acids residues in the active sites of CA II and CA IX. [GRAPHICS]