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 are evaluated against two human carbonic anhydrases (hCA I and II) and three CAs from the bacterial pathogen mycobacterium TB (mtCA1-3). The findings indicate that molecules featuring triazolyl benzene-3-sulfonamide are significantly more selective for mtCA 1-3 than hCA I and II. In contrast, across the generated molecules, benzofuran with triazolyl benzene-4-sulfonamide demonstrates greater selectivity for hCA II than mtCAs. Among these compounds, 3F4 shows the greatest suppression of mtCA2, with a Ki value of 0.0052 μM. 4F1 demonstrates 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 show minimum inhibitory concentration values for Mtb H37Rv strain inhibition in the range of moderate to good with 4-128 μg mL.