Carbonic anhydrases facilitate the interconversion of water and carbon dioxide to bicarbonate ions and protons (EC 4.2.1.1), with over a dozen gene products identified in man. The enzymes function in acid-base balance and the movement of carbon dioxide and water. They are targetted for therapeutic gain by particular antiglaucoma agents and diuretics.

* Key recommended reading is highlighted with an asterisk

Alterio V, Di Fiore A, D'Ambrosio K, Supuran CT, De Simone G. (2012) Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms?. Chem Rev, 112 (8): 4421-68. [PMID:22607219]

* Angeli A, Carta F, Nocentini A, Winum JY, Zalubovskis R, Akdemir A, Onnis V, Eldehna WM, Capasso C, Simone G et al.. (2020) Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment. Metabolites, 10 (10). DOI: 10.3390/metabo10100412 [PMID:33066524]

Cummins EP, Selfridge AC, Sporn PH, Sznajder JI, Taylor CT. (2014) Carbon dioxide-sensing in organisms and its implications for human disease. Cell Mol Life Sci, 71 (5): 831-45. [PMID:24045706]

Imtaiyaz Hassan M, Shajee B, Waheed A, Ahmad F, Sly WS. (2013) Structure, function and applications of carbonic anhydrase isozymes. Bioorg Med Chem, 21 (6): 1570-82. [PMID:22607884]

* Kumar S, Rulhania S, Jaswal S, Monga V. (2021) Recent advances in the medicinal chemistry of carbonic anhydrase inhibitors. Eur J Med Chem, 209: 112923. [PMID:33121862]

* Mishra CB, Tiwari M, Supuran CT. (2020) Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?. Med Res Rev, 40 (6): 2485-2565. [PMID:32691504]

Sjöblom M. (2011) Duodenal epithelial sensing of luminal acid: role of carbonic anhydrases. Acta Physiol (Oxf), 201 (1): 85-95. [PMID:20632999]

Supuran CT. (2017) Advances in structure-based drug discovery of carbonic anhydrase inhibitors. Expert Opin Drug Discov, 12 (1): 61-88. [PMID:27783541]

Supuran CT. (2018) Carbonic anhydrase activators. Future Med Chem, 10 (5): 561-573. [PMID:29478330]

* Supuran CT. (2020) Exploring the multiple binding modes of inhibitors to carbonic anhydrases for novel drug discovery. Expert Opin Drug Discov, 15 (6): 671-686. [PMID:32208982]

1. Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R. (2010) Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors. Bioorg Med Chem Lett, 20 (15): 4376-81. [PMID:20605094]

2. Congiu C, Onnis V, Deplano A, Balboni G, Dedeoglu N, Supuran CT. (2015) Synthesis of sulfonamides incorporating piperazinyl-ureido moieties and their carbonic anhydrase I, II, IX and XII inhibitory activity. Bioorg Med Chem Lett, 25 (18): 3850-3. [PMID:26233435]

3. Sethi KK, Vullo D, Verma SM, Tanç M, Carta F, Supuran CT. (2013) Carbonic anhydrase inhibitors: synthesis and inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety. Bioorg Med Chem, 21 (19): 5973-82. [PMID:23965175]

4. Temperini C, Cecchi A, Scozzafava A, Supuran CT. (2009) Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem, 17 (3): 1214-21. [PMID:19119014]