Novel sulfonamides bearing pyrrole and pyrrolopyrimidine moieties as carbonic anhydrase inhibitors: Synthesis, cytotoxic activity and molecular modeling

Abstract

Novel pyrrole and pyrrolopyrimidine scaffold-based sulfonamides were designed and synthesized. The carbonic anhydrase (CA) inhibition ability of all derivatives was assessed against the human (h) cytosolic isoforms hCA I and II and the transmembrane, tumor-associated isoforms hCA IX and XII. Some of these sulfonamides were 6-8 fold more potent than the reference drug acetazolamide (AZA, KiCombining double low line 5.7 nM)) against hCA XII showing subnanomolar activity. The in vitro cytotoxicity of these derivatives was evaluated against MCF-7, where some derivatives were more cytotoxic than doxorubicin (IC50Combining double low line 8.02 1/4M) displaying IC50values between 6.46 and 7.56 1/4M. Docking of these sulfonamides with CA XII was performed and their binding modes were comparable with that of AZA.