Exploration of 3‐substituted benzofuran‐tethered sulfamoyl triazoles as carbonic anhydrase inhibitors: Design, synthesis and biological evaluation

This study reports the design and synthesis of benzofuran‐tethered sulfamoyl triazoles. These compounds were evaluated against two human carbonic anhydrases (hCA I and II) and three carbonic anhydrases from the bacterial pathogen Mycobacterium TB, (mtCA1–3). The findings indicated that molecules featuring triazolyl benzene‐3‐sulfonamide were significantly more selective for mtCA 1–3 than hCA I and II. In contrast, across the generated molecules, benzofuran with triazolyl benzene‐4‐sulfonamide demonstrated greater selectivity for hCA II than mtCAs. Among these compounds, 3F4 showed the greatest suppression of mtCA2, with a Ki value of 0.0052 µM. 4F1 demonstrated essential and focused inhibition of hCA II, with a Ki value of 0.0094 µM, Compound 3F4 is 439 times more selective to mtCA2 than hCA I, and 47 times more selective than hCAII. Additionally, when examined for antitubercular activity, these compounds showed MIC values for Mtb H37Rv strain inhibition in the range of moderate to good with 4‐128 µg/mL.