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

作者：Chandak Navneet; Ceruso Mariangela; Supuran Claudiu T^*; Sharma Pawan K^*

来源：Bioorganic & Medicinal Chemistry, 2016, 24(13): 2882-2886.

DOI：10.1016/j.bmc.2016.04.052

• Sulfonamide
• Coumarin
• Human carbonic anhydrase isoforms I, II, IX, XII
• Acetazolamide
• Synergistic inhibition

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.

• 出版日期2016-7-1