Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoforms IX and XII

• Four novel sulfonamide bearing coumarin scaffolds were designed and synthesized.
• Their inhibition potential was evaluated against human CA I, II, IX and XII.
• Compounds found to be selective inhibitors of tumor associated hCAs IX & XII.
• Inhibition results compared to antitumor drug acetazolamide and found promising.

Four novel scaffolds consisting of total 24 compounds (1a–1o, 2a–2c, 3a–3c and 4a–4c) bearing aromatic sulfonamide and coumarin moieties connected through various linkers were synthesized in order to synergize the inhibition potential of both the moieties against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). All compounds were found to be potent inhibitors of tumor associated hCA IX & XII while at the same time required large amounts to inhibit off-targeted housekeeping hCA I & II. Selectivity was more pronounced against hCA II over I, and hCA XII over IX. Results were compared with antitumor drug acetazolamide. One derivative 2b of series 2 was found to be a better selective inhibitor of hCA IX and XII.

Sulfonamide bearing coumarin scaffolds showed synergistic inhibition potential against tumor associated hCA IX and XII much better than omnipresent off-targeted hCA I and II.Figure optionsDownload as PowerPoint slide