Zinc Binding Functions in the Design of Carbonic Anhydrase Inhibitors

Drug Design of Zinc-Enzyme Inhibitors: Functional, Structural, and Disease Applications

Volumn , Issue , 2009, Pages 39-72

  Winum, Jean Yves ^a   Montero, Jean Louis ^a   Scozzafava, Andrea ^b   Supuran, Claudiu T ^b  

^a INSTITUT CHARLES GERHARDT   (France)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

Sulfamide motif in CAI design; Sulfonamides as carbonic anhydrase inhibitors; Zinc binding functions in carbonic anhydrase inhibitor (CAI) design

Indexed keywords

EID: 77949344262     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470508169.ch3     Document Type: Chapter

References (62)

1. Supuran, C. T. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 2008, 7, 168-181.
2. Scozzafava, A.; Mastrolorenzo, A.; Supuran, C. T. Carbonic anhydrase inhibitors and activators and their use in therapy. Expert Opin. Ther. Patents 2006, 16, 1627-1664.
3. Supuran, C. T.; Scozzafava, A.; Conway, J., Eds. Carbonic Anhydrase: Its Inhibitors and Activators; CRC Press: Boca Raton, FL, 2004; pp 1-376, and references cited therein.
4. Supuran, C. T.; Scozzafava, A.; Casini, A. Carbonic anhydrase inhibitors. Med. Res. Rev. 2003, 23, 146-189.
5. Supuran, C. T.; Scozzafava, A. Carbonic anhydrases as targets for medicinal chemistry. Bioorg. Med. Chem. 2007, 15, 4336-4350.
6. Supuran, C. T. Carbonic anhydrases: an overview. Curr. Pharm. Des. 2008, 14, 603-614.
7. Winum, J.-Y.; Scozzafava, A.; Montero, J.-L.; Supuran, C. T. Design of zinc binding functions for carbonic anhydrase inhibitors. Curr. Pharm. Des. 2008, 14, 615-621.
8. Winum, J.Y.; Scozzafava, A.; Montero, J. L.; Supuran, C.T. Metal binding functions in the design of carbonic anhydrase inhibitors. Curr. Top. Med. Chem. 2007, 7, 835-848.
9. Winum, J.-Y.; Scozzafava, A.; Montero, J.-L.; Supuran, C. T. New zinc binding motifs in the design of selective carbonic anhydrase inhibitors. Mini Rev. Med. Chem. 2006, 6, 921-936.
10. Mann, T.; Keilin, D. Sulphanilamide as a specific carbonic anhydrase inhibitor. Nature 1940, 146, 164-165.
11. Mincione, F.; Scozzafava, A.; Supuran, C. T. The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr. Pharm. Des. 2008, 14, 649-654.
12. Abbate, F.; Casini, A.; Owa, T.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg. Med. Chem. Lett. 2004, 14, 217-223.
13. De Simone, G.; Di Fiore, A.; Menchise, V.; Pedone, C.; Antel, J.; Casini, A.; Scozzafava, A.; Wurl, M.; Supuran, C. T. Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg. Med. Chem. Lett. 2005, 15, 2315-2320.
14. Abbate, F.; Coetzee, A.; Casini, A.; Ciattini, S.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. Bioorg. Med. Chem. Lett. 2004, 14, 337-341.
15. Weber, A.; Casini, A.; Heine, A.; Kuhn, D.; Supuran, C. T.; Scozzafava, A.; Klebe, G. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. J. Med. Chem. 2004, 47, 550-557.
16. Di Fiore, A.; Pedone, C.; D'Ambrosio, K.; Scozzafava, A.; De Simone, G.; Supuran, C. T. Carbonic anhydrase inhibitors: valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II ''selective'' inhibitor celecoxib. Bioorg. Med. Chem. Lett. 2006, 16, 437-442.
17. Winum, J.-Y.; Rami, M.; Scozzafava, A.; Montero, J.-L.; Supuran, C. Carbonic anhydrase IX: a new druggable target for the design of antitumor agents. Med. Res. Rev. 2008, 28, 445-463.
18. De Simone, G.; Vitale, R. M.; Di Fiore, A.; Pedone, C.; Scozzafava, A.; Montero, J.-L.; Winum, J.-Y.; Supuran, C.-T. Carbonic anhydrase inhibitors: hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX. J. Med. Chem. 2006, 49, 5544-5551.
19. Winum, J.-Y.; Poulsen, S. A.; Supuran, C.-T. Therapeutic application of glycosidic carbonic anhydrase inhibitors. Med. Res. Rev. 2009, 29, 419-435.
20. Winum, J.-Y.; Casini, A.; Mincione, F.; Starnotti, M.; Montero, J.-L.; Scozzafava, A.; Supuran, C.-T. Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg. Med. Chem. Lett. 2004, 14, 225-229.
21. Di Fiore, A.; Scozzafava, A.; Winum, J.-Y.; Montero, J.-L.; Pedone, C.; Supuran, C. T.; De Simone, G. Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosylsulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties. Bioorg. Med. Chem. Lett. 2007, 17, 1726-1731.
22. Winum, J.-Y.; Scozzafava, A.; Montero, J.-L.; Supuran, C. T. Sulfamates and their therapeutic potential. Med. Res. Rev. 2005, 25, 186-228.
23. Winum, J.-Y.; Scozzafava, A.; Montero, J.-L.; Supuran, C. T. Therapeutic applications of sulfamates. Expert Opin. Ther. Patents 2004, 14, 1273-1308.
24. Briganti, F.; Pierattelli, A.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. Part 37. Novel classes of isozyme I and II inhibitors and their mechanism of action. Kinetic and spectroscopic investigations on native and cobalt-substituted enzymes. Eur. J. Med. Chem. 1996, 31, 1001-1010.
25. Abbate, F.; Supuran, C. T.; Scozzafava, A.; Orioli, P.; Stubbs, M. T.; Klebe, G. Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: role of hydrogen-bonding networks in ligand binding and drug design. J. Med. Chem. 2002, 45, 3583-3587.
26. Lo, Y. S.; Nolan, J. C.; Maren, T. H.; Welstead, W. J.; Gripshover, D. F.; Shamblee, D. A. Synthesis and physiochemical properties of sulfamate derivatives as topical antiglaucoma agents. J. Med. Chem. 1992, 35, 4790-4794.
27. Brechue, W. F.; Maren, T. H. Carbonic anhydrase inhibitory activity and ocular pharmacology of organic sulfamates. J. Pharm. Exp. Ther. 1992, 264, 670-675.
28. Maryanoff, B. E.; Nortey, S. O.; Gardocki, J. F.; Shank, R. P.; Dodgson, S. P. Anticonvulsant O-alkyl sulfamates. 2,3:4,5-Bis-O-(1-methyl ethylidene)-beta-D-fructopyranose sulfamate and related compounds. J. Med. Chem. 1987, 30, 880-887.
29. Maryanoff, B. E.; Costanzo, M. J.; Nortey, S. O.; Greco, M. N.; Shank, R. P.; Schupsky, J. J.; Ortegon, M. P.; Vaught, J. L. Structure-activity studies on anticonvulsant sugar sulfamates related to topiramate. Enhanced potency with cyclic sulfate derivatives. J. Med. Chem. 1998, 41, 1315-1343.
30. Recacha, R.; Costanzo, M. J.; Maryanoff, B. E.; Chattopadhyay, D. Crystal structure of human carbonic anhydrase II complexed with an anti-convulsant sugar sulphamate. Biochem. J. 2002, 361, 437-441.
31. Casini, A.; Antel, J.; Abbate, F.; Scozzafava, A.; David, S.; Waldeck, H.; Schafer, S.; Supuran, C. T. Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg. Med. Chem. Lett. 2003, 13, 841-845.
32. Nussbaumer, P.; Billich, A. Steroid sulfatase inhibitors. Expert Opin. Ther. Patents 2003, 13, 605-625.
33. Vicker, N.; Ho, Y.; Robinson, J.;Woo, L. L.; Purohit, A.; Reed,M. J.; Potter, B. V. Docking studies of sulphamate inhibitors of estrone sulfatase in human carbonic anhydrase II. Bioorg. Med. Chem. Lett. 2003, 13, 863-865.
34. Ho, Y. T.; Purohit, A.; Vicker, N.; Newman, S. P.; Robinson, J. J.; Leese, M. P.; Ganeshapillai, D.; Woo, L. W. L.; Potter, B. V.; Reed, M. J. Inhibition of carbonic anhydrase II by steroidal and non-steroidal sulfamates. Biochem. Biophys. Res. Commun. 2003, 305, 909-914.
35. Abbate, F.;Winum, J.Y.; Potter, B. V.; Casini, A.; Montero, J. L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid sulfatase. Bioorg. Med. Chem. Lett. 2004, 14, 231-234.
36. Winum, J. Y.; Vullo, D.; Casini, A.; Montero, J.-L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. Inhibition of cytosolic isozymes I and II and transmembrane, tumor-associated isozyme IX with sulfamates including EMATE also acting as steroid sulfatase inhibitors. J. Med. Chem. 2003, 46, 2197-2204.
37. Winum, J. Y.; Vullo, D.; Casini, A.; Montero, J. L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: inhibition of transmembrane, tumor-associated isozyme IX, and cytosolic isozymes I and II with aliphatic sulfamates. J. Med. Chem. 2003, 46, 5471-5477.
38. Thiry, A.; Dogné, J. M.; Masereel, B.; Supuran, C. T. Targeting tumor-associated carbonic anhydrase IX in cancer therapy. Trends Pharmacol. Sci. 2006, 27, 566-573.
39. Winum, J.-Y.; Pastorekova, S.; Jakubickova, L.; Montero, J.-L.; Scozzafava, A.; Pastorek, J.; Vullo, D.; Innocenti, A.; Supuran, C. T. Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with bis-sulfamates. Bioorg. Med. Chem. Lett. 2005, 15, 579-584.
40. Winum, J.-Y.; Scozzafava, A.; Montero, J.-L.; Supuran, C.-T. Therapeutic potential of sulfamides as enzyme inhibitors. Med. Res. Rev. 2006, 26, 767-792.
41. Winum, J.-Y.; Scozzafava, A.; Montero, J.-L.; Supuran, C.-T. The sulfamide motif in the design of enzyme inhibitors. Expert Opin. Ther. Patents 2006, 16, 27-47.
42. Scozzafava, A.; Banciu, M. D.; Popescu, A.; Supuran, C. T. Carbonic anhydrase inhibitors: inhibition of isozymes I, II, and IV by sulfamide and sulfamic acid derivatives. J. Enzyme Inhib. 2000, 15, 443-453.
43. Casini, A.; Winum, J.-Y.; Montero, J.-L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: inhibition of cytosolic isozymes I and II with sulfamide derivatives. Bioorg. Med. Chem. Lett. 2003, 13, 837-840.
44. Winum, J.-Y.; Toupet, L.; Barragan, V.; Dewynter, G.; Montero, J.-L. N-(tert-Butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-ylsulfonyl] azanide: a new sulfamyolating agent. Structure and reactivity toward amines. Org. Lett. 2001, 3, 2241-2243.
45. Winum, J.-Y.; Cecchi, A.; Montero, J.-L.; Innocenti, A.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. Synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with boron-containing sulfonamides, sulfamides, and sulfamates: toward agents for boron neutron capture therapy of hypoxic tumors. Bioorg. Med. Chem. Lett. 2005, 15, 3302-3306.
46. Winum, J.-Y.; Temperini, C.; El Cheikh, K.; Innocenti, A.; Vullo, D.; Ciattini, S.; Montero, J.-L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J. Med. Chem. 2006, 49, 7024-7031.
47. Krebs, H. A. Inhibition of carbonic anhydrase by sulfonamides. Biochem. J. 1948, 43, 525-528.
48. Mincione, F.; Menabuoni, L.; Briganti, F.; Mincione, G.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. Inhibition of isozymes I, II and IV with N-hydroxysulfonamides. A novel class of intraocular pressure lowering agents. J. Enzyme Inhib. 1998, 13, 267-284.
49. Supuran, C. T.; Scozzafava, A.; Briganti, F. Carbonic anhydrase inhibitors: N-cyanosulfonamides: a newclass of high affinity isozyme II and IVinhibitors. J. Enzyme Inhib. 1999, 14, 289-306.
50. Fenesan, I.; Popescu, R.; Scozzafava, A.; Crucin, V.; Mateiciuc, E.; Bauer, R.; Ilies, M. A.; Supuran, C. T. Carbonic anhydrase inhibitors. Phosphoryl sulfonamides. A new class of high affinity inhibitors of isozyme I. J. Enzyme Inhib. 2000, 15, 297-310.
51. Supuran, C. T.; Scozzafava, A. Applications of carbonic anhydrase inhibitors and activators in therapy. Expert Opin. Ther.Patents 2002, 12, 217-242.
52. Scolnik, L. R.; Clements, A. M.; Liao, J.; Crenshaw, L.; Hellberg, M.; May, J.; Dean, D. R.; Christianson, D. W. Novel binding mode of hydroxamate inhibitors to human carbonic anhydrase II. J. Am. Chem. Soc. 1997, 119, 850-851.
53. Scozzafava, A.; Supuran, C. T. Hydroxyurea is a carbonic anhydrase inhibitor. Bioorg. Med. Chem. 2003, 11, 2241-2246.
54. Temperini, C.; Innocenti, A.; Scozzafava, A.; Supuran, C. T. N-Hydroxyurea: a versatile zinc binding function in the design of metalloenzyme inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 4316-4320.
55. Briganti, F.; Pierattelli, A.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. Part 37. Novel classes of isozyme I and II inhibitors and their mechanism of action. Kinetic and spectroscopic investigations on native and cobalt-substituted enzymes. Eur. J. Med. Chem. 1996, 31, 1001-1010.
56. Abbate, F.; Supuran, C. T.; Scozzafava, A.; Orioli, P.; Stubbs, M. T.; Klebe, G. Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: role of hydrogen-bonding networks in ligand binding and drug design. J. Med. Chem. 2002, 45, 3583-3587.
57. Temperini, C.; Winum, J.-Y.; Montero, J.-L.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. The X-ray crystal structure of the adduct ofN-hydroxysulfamide with the isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors. Bioorg. Med. Chem. Lett. 2007, 17, 2797-2801.
58. Winum, J. Y.; Innocenti, A.; Nasr, J.; Montero, J.-L.; Scozzafava, A.; Vullo, D.; Supuran, C. T. Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, IX, and XII with N-hydroxysulfamides: a new zincbinding function in the design of inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 2353-2358.
59. Bonnac, L.; Innocenti, A.; Winum, J.-Y.; Casini, A.; Montero, J.-L.; Scozzafava, A.; Barragan, V.; Supuran, C. T. Carbonic anhydrase inhibitors: aliphatic N-phosphorylated sulfamate. A novel zinc anchoring group leading to nanomolar inhibitors. J. Enzyme Inhib. Med. Chem. 2004, 19, 287-291.
60. Rusconi, S.; Innocenti, A.; Vullo, D.; Mastrolorenzo, A.; Scozzafava, A.; Supuran, C. T. Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, Vand IX with phosphates, carbamoyl phosphate, and the phosphonate antiviral drug foscarnet. Bioorg. Med. Chem. Lett. 2004, 14, 5763-5767.
61. Temperini, C.; Innocenti, A.; Guerri, A.; Scozzafava, A.; Rusconi, S.; Supuran, C. T. Phosph(on)ate as a zinc binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I. Bioorg. Med. Chem. Lett. 2007, 17, 5763-5767.
62. Winum, J.-Y.; Innocenti, A.; Gagnard, V.; Montero, J.-L.; Scozzafava, A.; Vullo, D.; Supuran, C. T. Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, Vand IX with organic phosphates and phosphonates. Bioorg. Med. Chem. Lett. 2005, 15, 1683-1686.