Synthesis and human carbonic anhydrase I, II, VA, and XII inhibition with novel amino acid-sulphonamide conjugates

• Published in: Journal of enzyme inhibition and medicinal chemistry 2020-01, Vol.35 (1), p.489-497
• Main Authors: Küçükbay, Hasan, Buğday, Nesrin, Küçükbay, F. Zehra, Ageli, Andrea, Bartolucci, Gianluca, Supuran, Claudiu T.
• Format: Article
• Language: English
• Subjects: Acetazolamide; amino acid; Amino acids; Amino Acids - chemical synthesis; Amino Acids - chemistry; Amino Acids - pharmacology; Carbonic anhydrase; Carbonic anhydrase I; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrases - metabolism; conjugate; Humans; inhibitor; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Isoforms; Molecular Structure; NMR; Nuclear magnetic resonance; Research Paper; Sulfonamides; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; sulphonamide
• ISSN: 1475-6366; 1475-6374; 1475-6374
• DOI: 10.1080/14756366.2019.1710503

A series of amino acid-sulphonamide conjugates was prepared through benzotriazole mediated coupling reactions and characterised by 1 H-NMR, 13 C-NMR, MS, and FTIR spectroscopic techniques as well as elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was determined against four human (h) isoforms, hCA I, hCA II, hCA VA, and hCA XII. Most of the synthesised compounds showed effective in vitro CA inhibitory properties. The new amino acid-sulphonamide conjugates showed potent inhibitory activity against hCA II, some of them at subnanomolar levels, exhibiting more effective inhibitory activity compared to the standard drug acetazolamide. Some of these sulphonamides were also found to be effective inhibitors of hCA I, hCA VA, and hCA XII, with activity from the low to high nanomolar range.