Ccarbonic Anhydrase Inhibitors: Bioreductive Nitro-Containing Sulfonamides With Selectivity For Targeting The Tumor Associated Isoforms Ix And Xii(828 views) D'Ambrosio K, Vitale R, Dogne J, Masereel B, Innocenti A, Scozzafava A, De Simone G, Supuran CT
J Med Chem (ISSN: 1520-4804, 0022-2623, 0022-2623print), 2008 Jun 12; 51(11): 3230-3237.
Keywords: 2 Chloro 5 Nitro Benzenesulfonamide, Carbonate Dehydratase, Carbonate Dehydratase Inhibitor, Nitro Derivative, Article, Crystal Structure, Drug Selectivity, Drug Structure, Drug Targeting, Enzyme Inhibition, Hypoxia, Molecular Dynamics, Molecular Model, Reduction, Sequence Alignment, Tumor, X Ray Crystallography, Amino Acid Sequence, Antigens, Neoplasm, Carbonic Anhydrase I, Carbonic Anhydrase Inhibitors, Conserved Sequence, X-Ray, Humans, Isoenzymes, Molecular Sequence Data, Nitro Compounds, Structure-Activity Relationship,
Affiliations: *** IBB - CNR ***
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy
Istituto di Chimica e Biomolecolare-CNR, via Campi Flegrei 34, 80078, Pozzuoli, Italy
Drug Design and Discovery Center, University of Namur, 61 rue de Bruxelles, 5000 Namur, Belgium
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy
Universit degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy
References: Supuran, C.T., Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators (2008) Nat. Rev. Drug Discovery, 7, pp. 168-18
Supuran, C.T., Scozzafava, A., Carbonic anhydrases as targets for medicinal chemistry (2007) Bioorg. Med. Chem, 15, pp. 4336-4350
Thiry, A., Dogné, J.M., Masereel, B., Supuran, C.T., Targeting tumor-associated carbonic anhydrase IX in cancer therapy (2006) Trends Pharmacol. Sci, 27, pp. 566-573
Pastorekova, S., Kopacek, J., Pastorek, J., Carbonic Anhydrase Inhibitors and the Management of Cancer (2007) Curr. Top. Med. Chem, 7, pp. 865-878
Alterio, V., Vitale, R.M., Monti, S.M., Pedone, C., Scozzafava, A., Cecchi, A., De Simone, G., Supuran, C.T., Carbonic Anhydrase Inhibitors: X-ray and Molecular Modeling Study for the Interaction of a Fluorescent Antitumor Sulfonamide with Isozyme II and IX (2006) J. Am. Chem. Soc, 128, pp. 8329-8335
Menchise, V., De Simone, G., Alterio, V., Di Fiore, A., Pedone, C., Scozzafava, A., Supuran, C.T., Carbonic Anhydrase Inhibitors: Stacking with Phe131 Determines Active Site Binding Region of Inhibitors As Exemplified by the X-ray Crystal Structure of a Membrane-impermeant Antitumor Sulfonamide Complexed with Isozyme II (2005) J. Med. Chem, 48, pp. 5721-5727
De Simone, G., Vitale, R.M., Di Fiore, A., Pedone, C., Scozzafava, A., Montera, J.L., Winum, J.Y., Supuran, C.T., Carbonic Anhydrase Inhibitors: Hypoxia-Activatable Sulfonamides Incorporating Disulfide Bonds that Target the Tumor-Associated Isoform IX (2006) J. Med. Chem, 49, pp. 5544-5551
Raether, W., Hane, H., Nitroheterocyclic drugs with broad spectrum activity (2003) Parasitol. Res, 90, pp. S19-S39
Anderson, R.F., Shinde, S.S., Hay, M.P., Denny, W.A., Potentiation of the cytotoxicity of the anticancer agent tirapazamine by benzotriazine N-oxides: The role of redox equilibra (2006) J. Am. Chem. Soc, 128, pp. 245-249
Ljungkvist, A.S., Bussink, J., Kaanders, J.H., van der Kogel, A.J., Dynamics of tumor hypoxia measured with bioreductive hypoxic cell markers (2007) Radiat. Res, 167, pp. 127-145
Nutt, R., Vento, L.J., Ridinger, M.H.T., In Vivo Molecular Imaging Biomarkers: Clinical Pharmacology's new "PET (2007) Clin. Pharmacol. Ther, 81, pp. 792-795
Arteel, G.E., Raleigh, J.A., Bradford, B.U., Thurman, R.G., Acute alcohol produces hypoxia directly in rat liver tissue in vivo: Role of Kupffer cells (1996) Am. J. Physiol, 271, pp. G494-G500
Mallia, M.B., Mathur, A., Subramanian, S., Banerjee, S., Sarma, H.D., Venkatesh, M., A novel [99mTc=N]2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia (2005) Bioorg. Med. Chem. Lett, 15, pp. 3398-3401
Hanson, J., Dogné, J.M., Ghiotto, J., Moray, A.L., Kinsella, B.T., Pirotte, B., Design, synthesis, and SAR study of a series of N-alkyl-N′-[2-(aryloxy)-5-nitrobenzenesulfonyl]ureas and -cyanoguanidine as selective antagonists of the TPalpha and TPbeta isoforms of the human thromboxane A2 receptor (2007) J. Med. Chem, 50, pp. 3928-3936
Khalifah, R. G. The carbon dioxide hydration activity of carbonic anhydrase I. Stop-flow kinetic studies on the native human isoenzymes B and C. J. Biol. Chem. 1971, 246, 2561-2573Casini, A.
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, 841-845Winum, J.Y., Temperini, C., El Cheikh, K., Innocenti, A., Vullo, D., Ciattini, S., Montera, J.L., 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 (2006) J. Med. Chem, 49, pp. 7024-7031
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 (2007) Bioorg. Med. Chem. Lett, 17, pp. 2210-2215
AIterio, V., De Simone, G., Monti, S.M., Scozzafava, A., Supuran, C.T., Carbonic anhydrase inhibitors: Inhibition of human, bacterial, and archaeal isozymes with benzene-1,3-disulfonamides: solution and crystallographic studies (2007) Bioorg. Med. Chem. Lett, 17, pp. 4201-4207
Güzel, O., Temperini, C., Innocenti, A., Scozzafava, A., Salman, A., Supuran, C.T., Carbonic anhydrase inhibitors. Interaction of 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: Kinetic and X-ray crystallographic studies (2008) Bioorg. Med. Chem. Lett, 18, pp. 152-158
Casini, A., Abbate, F., Scozzafava, A., Supuran, C.T., Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a bis-sulfonamide: two heads are better than one (2003) Bioorg. Med. Chem. Lett, 13, pp. 2759-2763
Vullo, D., Innocenti, A., Nishimori, I., Pastorek, J., Scozzafava, A., Pastorekova, S., Supuran, C.T., Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides: A new target for the design of antitumor and antiglaucoma drugs (2005) Bioorg. Med. Chem. Lett, 15, pp. 963-969
Eriksson, A.E., Jones, T.A., Liljas, A., Refined structure of human carbonic anhydrase II at 2.0 Å resolution (1988) Proteins: Struct., Funct, 4, pp. 274-282
Otwinowski, Z., Minor, W., Processing of X-ray Diffraction Data Collected in Oscillation Mode (1997) Methods Enzymol, 276, pp. 307-326
Brünger, A.T., Adams, P.D., Clore, G.M., De Lano, W.L., Gros, P., Grosse-Kunstleve, R.W., Jiang, J.S., Warren, G.L., Crystallography & NMR system: A new software suite for macromolecular structure determination (1998) Acta Crystallogr., Sect. D: Biol Crystallogr, 54, pp. 905-921
Jones, T.A., Zou, J.Y., Cowan, S.W., Kjeldgaard, M., Improved methods for building protein models in electron density maps and the location of errors in these models (1991) Acta Crystallogr., Sect. A: Found. Crystallogr, 47, pp. 110-119
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., PROCHECK: A program to check the stereochemical quality of protein structures (1993) J. Appl. Crystallogr, 26, pp. 283-291
Boeckmann, B., Bairoch, A., Apweiler, R., Blatter, M.C., Estreicher, A., Gasteiger, E., Martin, M.J., Schneider, M., The SWISS-PROT protein knowledge-base and its supplement TrEMBL in 2003 (2003) Nucleic Acids Res, 31, pp. 365-370
Whittington, D.A., Grubb, J.H., Waheed, A., Shah, G.N., Sly, W.S., Christianson, D.W., Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: Implications for selective inhibition of membrane-associated isozymes (2004) J. Biol. Chem, 279, pp. 7223-7228
Sali, A., Blundell, T.L., Comparative protein modelling by satisfaction of spatial restraints (1993) J. Mol. Biol, 234, pp. 779-815
Bowie, J.U., Luthy, R., Eisenberg, D., A method to identify protein sequences that fold into a known three-dimensional structure (1991) Science, 253, pp. 164-170
Case, D.A., Darden, T.A., Cheatham III, T.E., Simmerling, C.L., Wang, J., Duke, R.E., Luo, R., Kollman, P.A., (2006) AMBER 9, , University of California: San Francisco
Wang, J., Cieplak, P., Kollman, P.A., How Well Does a RESP (Restrained Electrostatic Potential) Model Do in Calculating the Conformational Energies of Organic and Biological Molecules? (2000) J. Comput. Chem, 21, pp. 1049-1074
Kollman, P. A. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: the RESP model. J. Phys. Chem. 1993, 97, 10269-10280Schmidt, M.W., Baldridge, K.K., Boatz, J.A., Elbert, S.T., Gordon, M.S., Jensen, J.J., Koseki, S., Montgomery, J.A., General Atomic and Molecular Electronic Structure System (1993) J. Comput. Chem, 14, pp. 1347-1363
Suarez, D., Merz, K.M., Molecular Dynamics Simulations of the Mononuclear Zinc-β-lactamase from Bacillus cereus (2001) J. Am. Chem. Soc, 123, pp. 3759-3770
Hoops, S.C., Anderson, K.W., Merz, K.M., Force field design for metalloproteins (1991) J. Am. Chem. Soc, 113, pp. 8262-8270
Ryckaert, J.-P., Ciccotti, G., Berendsen, H.J.C., Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes (1977) J. Comput. Phys, 23, pp. 327-341
Koradi, R., Billeter, M., Wuthrich, K., MOLMOL: A program for display and analysis of macromolecular structures (1996) J. Mol. Graphics, 14, pp. 51-55
Supuran, C. T., Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators (2008) Nat. Rev. Drug Discovery, 7, pp. 168-18
Supuran, C. T., Scozzafava, A., Carbonic anhydrases as targets for medicinal chemistry (2007) Bioorg. Med. Chem, 15, pp. 4336-4350
Thiry, A., Dogn, J. M., Masereel, B., Supuran, C. T., Targeting tumor-associated carbonic anhydrase IX in cancer therapy (2006) Trends Pharmacol. Sci, 27, pp. 566-573
Anderson, R. F., Shinde, S. S., Hay, M. P., Denny, W. A., Potentiation of the cytotoxicity of the anticancer agent tirapazamine by benzotriazine N-oxides: The role of redox equilibra (2006) J. Am. Chem. Soc, 128, pp. 245-249
Ljungkvist, A. S., Bussink, J., Kaanders, J. H., van der Kogel, A. J., Dynamics of tumor hypoxia measured with bioreductive hypoxic cell markers (2007) Radiat. Res, 167, pp. 127-145
Arteel, G. E., Raleigh, J. A., Bradford, B. U., Thurman, R. G., Acute alcohol produces hypoxia directly in rat liver tissue in vivo: Role of Kupffer cells (1996) Am. J. Physiol, 271, pp. G494-G500
Mallia, M. B., Mathur, A., Subramanian, S., Banerjee, S., Sarma, H. D., Venkatesh, M., A novel [99mTc=N] 2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia (2005) Bioorg. Med. Chem. Lett, 15, pp. 3398-3401
Hanson, J., Dogn, J. M., Ghiotto, J., Moray, A. L., Kinsella, B. T., Pirotte, B., Design, synthesis, and SAR study of a series of N-alkyl-N - [2- (aryloxy) -5-nitrobenzenesulfonyl] ureas and -cyanoguanidine as selective antagonists of the TPalpha and TPbeta isoforms of the human thromboxane A2 receptor (2007) J. Med. Chem, 50, pp. 3928-3936
G zel, O., Temperini, C., Innocenti, A., Scozzafava, A., Salman, A., Supuran, C. T., Carbonic anhydrase inhibitors. Interaction of 2- (hydrazinocarbonyl) -3-phenyl-1H-indole-5-sulfonamide with 12 mammalian isoforms: Kinetic and X-ray crystallographic studies (2008) Bioorg. Med. Chem. Lett, 18, pp. 152-158
Eriksson, A. E., Jones, T. A., Liljas, A., Refined structure of human carbonic anhydrase II at 2. 0 resolution (1988) Proteins: Struct., Funct, 4, pp. 274-282
Br nger, A. T., Adams, P. D., Clore, G. M., De Lano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Warren, G. L., Crystallography & NMR system: A new software suite for macromolecular structure determination (1998) Acta Crystallogr., Sect. D: Biol Crystallogr, 54, pp. 905-921
Jones, T. A., Zou, J. Y., Cowan, S. W., Kjeldgaard, M., Improved methods for building protein models in electron density maps and the location of errors in these models (1991) Acta Crystallogr., Sect. A: Found. Crystallogr, 47, pp. 110-119
Laskowski, R. A., MacArthur, M. W., Moss, D. S., Thornton, J. M., PROCHECK: A program to check the stereochemical quality of protein structures (1993) J. Appl. Crystallogr, 26, pp. 283-291
Whittington, D. A., Grubb, J. H., Waheed, A., Shah, G. N., Sly, W. S., Christianson, D. W., Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: Implications for selective inhibition of membrane-associated isozymes (2004) J. Biol. Chem, 279, pp. 7223-7228
Bowie, J. U., Luthy, R., Eisenberg, D., A method to identify protein sequences that fold into a known three-dimensional structure (1991) Science, 253, pp. 164-170
Case, D. A., Darden, T. A., Cheatham III, T. E., Simmerling, C. L., Wang, J., Duke, R. E., Luo, R., Kollman, P. A., (2006) AMBER 9, , University of California: San Francisco
Hoops, S. C., Anderson, K. W., Merz, K. M., Force field design for metalloproteins (1991) J. Am. Chem. Soc, 113, pp. 8262-8270
Ryckaert, J. -P., Ciccotti, G., Berendsen, H. J. C., Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes (1977) J. Comput. Phys, 23, pp. 327-341
Ccarbonic Anhydrase Inhibitors: Bioreductive Nitro-Containing Sulfonamides With Selectivity For Targeting The Tumor Associated Isoforms Ix And Xii
2-Substituted-5-nitro-benzenesulfonamides incorporating a large variety of secondary/tertiary amines were explored as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4. 2. 1. 1), with the aim of designing bioreductive inhibitors targeting the hypoxia overexpressed, tumor-associated isozymes. The compounds were ineffective inhibitors of the cytosolic isoform I, showed a better inhibition of the physiologically relevant CA II (KIs of 8. 8-4975 nM), and strongly inhibited the tumor-associated CA IX and XII (K Is of 5. 4-653 nM). Some of these compounds showed excellent selectivity ratios for the inhibition of the tumor-associated isozymes over the cytosolic ones (in the range of 10-1395). The X-ray crystal structure of the adduct of hCA II with the lead molecule 2-chloro-5-nitro-benzenesulfonamide as well as molecular modeling studies for interaction with hCA IX afforded a better understanding of factors governing the discrimination of the two isoforms for this type of bioreductive compound targeting specifically hypoxic tumors. 2008 American Chemical Society
Ccarbonic Anhydrase Inhibitors: Bioreductive Nitro-Containing Sulfonamides With Selectivity For Targeting The Tumor Associated Isoforms Ix And Xii