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S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases.

Lopez M, Paul B, Hofmann A, Morizzi J, Wu QK, Charman SA, Innocenti A, Vullo D, Supuran CT, Poulsen SA
J Med Chem 52 6421-32 (2009)
Related entries: 3hkq, 3hkt, 3hku

Cited: 21 times
EuropePMC logo PMID: 19827837

Abstract

In this paper, we present a new class of carbonic anhydrase (CA) inhibitor that was designed to selectively target the extracellular domains of the cancer-relevant CA isozymes. The aromatic moiety of the classical zinc binding sulfonamide CA inhibitors is absent from these compounds and instead they incorporate a hydrophilic mono- or disaccharide fragment directly attached to the sulfonamide group to give S-glycosyl primary sulfonamides (1-10). The inhibition properties of these compounds at the physiologically abundant human CA isozymes I and II and cancer-associated IX and XII were determined, and all compounds had moderate potency with K(i)s in the micromolar range. We present the crystal structures of anomeric sulfonamides 4, 7, and 10 and the sugar sulfamate drug topiramate in complex with human recombinant CA II. From these structures, we have obtained valuable insights into ligand-protein interactions of these novel carbohydrate-based sulfonamides with CA.

Reviews citing this publication (7)

  1. Experimental Carbonic Anhydrase Inhibitors for the Treatment of Hypoxic Tumors. Supuran CT. J Exp Pharmacol 12 603-617 (2020)
  2. Glycosidic carbonic anhydrase IX inhibitors: a sweet approach against cancer. Winum JY, Colinas PA, Supuran CT. Bioorg. Med. Chem. 21 1419-1426 (2013)
  3. Carbonic anhydrase inhibition as a cancer therapy: a review of patent literature, 2007 - 2009. Poulsen SA. Expert Opin Ther Pat 20 795-806 (2010)
  4. Probing the surface of human carbonic anhydrase for clues towards the design of isoform specific inhibitors. Pinard MA, Mahon B, McKenna R. Biomed Res Int 2015 453543 (2015)
  5. Inhibition of carbonic anhydrase IX targets primary tumors, metastases, and cancer stem cells: Three for the price of one. Supuran CT, Alterio V, Di Fiore A, D' Ambrosio K, Carta F, Monti SM, De Simone G. Med Res Rev 38 1799-1836 (2018)
  6. Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site. Singh S, Lomelino CL, Mboge MY, Frost SC, McKenna R. Molecules 23 (2018)
  7. Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design. Linkuvienė V, Zubrienė A, Manakova E, Petrauskas V, Baranauskienė L, Zakšauskas A, Smirnov A, Gražulis S, Ladbury JE, Matulis D. Q Rev Biophys 51 e10 (2018)

Articles citing this publication (14)

  1. Insights towards sulfonamide drug specificity in α-carbonic anhydrases. Aggarwal M, Kondeti B, McKenna R. Bioorg. Med. Chem. 21 1526-1533 (2013)
  2. Targeting hypoxic tumor cell viability with carbohydrate-based carbonic anhydrase IX and XII inhibitors. Morris JC, Chiche J, Grellier C, Lopez M, Bornaghi LF, Maresca A, Supuran CT, Pouysségur J, Poulsen SA. J. Med. Chem. 54 6905-6918 (2011)
  3. Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations. De Simone G, Langella E, Esposito D, Supuran CT, Monti SM, Winum JY, Alterio V. J Enzyme Inhib Med Chem 32 1002-1011 (2017)
  4. The first example of a significant active site conformational rearrangement in a carbonic anhydrase-inhibitor adduct: the carbonic anhydrase I-topiramate complex. Alterio V, Monti SM, Truppo E, Pedone C, Supuran CT, De Simone G. Org. Biomol. Chem. 8 3528-3533 (2010)
  5. A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX. Pinard MA, Aggarwal M, Mahon BP, Tu C, McKenna R. Acta Crystallogr F Struct Biol Commun 71 1352-1358 (2015)
  6. An overview of carbohydrate-based carbonic anhydrase inhibitors. Cuffaro D, Nuti E, Rossello A. J Enzyme Inhib Med Chem 35 1906-1922 (2020)
  7. From in situ to in vivo: an in situ click-chemistry-derived carbonic anhydrase II imaging agent for positron emission tomography. Mocharla VP, Walsh JC, Padgett HC, Su H, Fueger B, Weber WA, Czernin J, Kolb HC. ChemMedChem 8 43-48 (2013)
  8. Unexpected furanose/pyranose equilibration of N-glycosyl sulfonamides, sulfamides and sulfamates. Suthagar K, Polson MI, Fairbanks AJ. Org. Biomol. Chem. 13 6573-6579 (2015)
  9. Efficacious N-protection of O-aryl sulfamates with 2,4-dimethoxybenzyl groups. Reuillon T, Bertoli A, Griffin RJ, Miller DC, Golding BT. Org. Biomol. Chem. 10 7610-7617 (2012)
  10. P-glycoprotein-mediated chemoresistance is reversed by carbonic anhydrase XII inhibitors. Kopecka J, Rankin GM, Salaroglio IC, Poulsen SA, Riganti C. Oncotarget 7 85861-85875 (2016)
  11. Advances in Anti-Cancer Drug Development Targeting Carbonic Anhydrase IX and XII. Mboge MY, McKenna R, Frost SC. Top Anticancer Res 5 3-42 (2015)
  12. Synthesis and anti-mycobacterial activity of glycosyl sulfamides of arabinofuranose. Suthagar K, Fairbanks AJ. Org. Biomol. Chem. 14 1748-1754 (2016)
  13. Thiol-ene click chemistry for the synthesis of highly effective glycosyl sulfonamide carbonic anhydrase inhibitors. Saada MC, Ombouma J, Montero JL, Supuran CT, Winum JY. Chem. Commun. (Camb.) 49 5699-5701 (2013)
  14. The Glitazone Class of Drugs as Carbonic Anhydrase Inhibitors-A Spin-Off Discovery from Fragment Screening. Mueller SL, Chrysanthopoulos PK, Halili MA, Hepburn C, Nebl T, Supuran CT, Nocentini A, Peat TS, Poulsen SA. Molecules 26 3010 (2021)


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