Carbonic anhydrase inhibitory properties of novel benzylsulfamides using molecular modeling and experimental studies

• Six novel sulfamoylcarbamates derived from benzylamines were synthesized.
• Six sulfamides were synthesized from sulfamoylcarbamates.
• The synthesized compounds were evaluated for their carbonic anhydrase.
• All synthesized compounds showed effective inhibitory properties against hCA I and hCA II isoenzymes.
• Molecular modeling also showed inhibitory properties for the synthesized compound.

In this study, a series of sulfamoyl carbamates and sulfamide derivatives were synthesized. Six commercially available benzyl amines and BnOH were reacted with chlorosulfonyl isocyanate (CSI) to give sulfamoyl carbamates. Pd–C catalyzed hydrogenolysis reactions of carbamates afforded sulfamides. The inhibition effects of novel benzylsulfamides on the carbonic anhydrase I, and II isoenzymes (CA I, and CA II) purified from fresh human blood red cells were determined by Sepharose-4B-L-Tyrosine-sulfanilamide affinity chromatography. In vitro studies were shown that all of novel synthesized benzylsulfamide analogs inhibited, concentration dependently, both hCA isoenzyme activities. The novel benzylsulfamide compounds investigated here exhibited nanomolar inhibition constants against the two isoenzymes. Ki values were in the range of 28.48 ± 0.01–837.09 ± 0.19 nM and 112.01 ± 0.01–268.01 ± 0.22 nM for hCAI and hCA II isoenzymes, respectively. Molecular modeling approaches were also applied for studied compounds.

A series of sulfamoylcarbamates and sulfamides were evaluated for hCA I and hCA II inhibitory properties. Molecular modeling and experimental studies showed that all compounds are sufficiently active as carbonic anhydrase inhibitors.Figure optionsDownload as PowerPoint slide