2aw1 › Citations

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.

Di Fiore A, Pedone C, D'Ambrosio K, Scozzafava A, De Simone G, Supuran CT
Bioorg Med Chem Lett 16 437-42 (2006)
Cited: 51 times
EuropePMC logo PMID: 16290146

Abstract

The high resolution X-ray crystal structure of the adduct of human carbonic anhydrase (CA, EC 4.2.1.1) isoform II (hCA II) with the clinically used painkiller valdecoxib, acting as a potent CA II and cyclooxygenase-2 (COX-2) inhibitor, is reported. The ionized sulfonamide moiety of valdecoxib is coordinated to the catalytic Zn(II) ion with a tetrahedral geometry. The phenyl-isoxazole moiety of the inhibitor fills the active site channel and interacts with the side chains of Gln92, Val121, Leu198, Thr200, and Pro202. Its 3-phenyl group is located into a hydrophobic pocket, simultaneously establishing van der Waals interactions with the aliphatic side chain of various hydrophobic residues (Val135, Ile91, Val121, Leu198, and Leu141) and a strong offset face-to-face stacking interaction with the aromatic ring of Phe131 (the chi1 angle of which is rotated about 90 degrees with respect to what was observed in the structure of the native enzyme and those of other sulfonamide complexes). Celecoxib, a structurally related COX-2 inhibitor for which the X-ray crystal structure was reported earlier, binds in a completely different manner to hCA II as compared to valdecoxib. Celecoxib completely fills the entire CA II active site, with its trifluoromethyl group in the hydrophobic part of the active site and the p-tolyl moiety in the hydrophilic one, not establishing any interaction with Phe131. In contrast to celecoxib, valdecoxib was rotated about 90 degrees around the chemical bond connecting the benzensulfonamide and the substituted isoxazole ring allowing for these multiple favorable interactions. These different binding modes allow for the further drug design of various CA inhibitors belonging to the benzenesulfonamide class.

Reviews - 2aw1 mentioned but not cited (1)

  1. Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. Krishnamurthy VM, Kaufman GK, Urbach AR, Gitlin I, Gudiksen KL, Weibel DB, Whitesides GM. Chem Rev 108 946-1051 (2008)

Articles - 2aw1 mentioned but not cited (3)

  1. Primary mono- and bis-sulfonamides obtained via regiospecific sulfochlorination of N-arylpyrazoles: inhibition profile against a panel of human carbonic anhydrases. Krasavin M, Korsakov M, Ronzhina O, Tuccinardi T, Kalinin S, Tanç M, Supuran CT. J Enzyme Inhib Med Chem 32 920-934 (2017)
  2. Novel 8-Substituted Coumarins That Selectively Inhibit Human Carbonic Anhydrase IX and XII. Buran K, Bua S, Poli G, Önen Bayram FE, Tuccinardi T, Supuran CT. Int J Mol Sci 20 E1208 (2019)
  3. Identification of human cyclooxegenase-2 inhibitors from Cyperus scariosus (R.Br) rhizomes. Kakarla L, Mathi P, Allu PR, Rama C, Botlagunta M. Bioinformation 10 637-646 (2014)


Reviews citing this publication (14)

  1. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Supuran CT. Nat Rev Drug Discov 7 168-181 (2008)
  2. Structure-based drug discovery of carbonic anhydrase inhibitors. Supuran CT. J Enzyme Inhib Med Chem 27 759-772 (2012)
  3. How many carbonic anhydrase inhibition mechanisms exist? Supuran CT. J Enzyme Inhib Med Chem 31 345-360 (2016)
  4. NSAIDs inhibit tumorigenesis, but how? Gurpinar E, Grizzle WE, Piazza GA. Clin Cancer Res 20 1104-1113 (2014)
  5. Sulfonamides: a patent review (2008 - 2012). Carta F, Scozzafava A, Supuran CT. Expert Opin Ther Pat 22 747-758 (2012)
  6. Exploiting the hydrophobic and hydrophilic binding sites for designing carbonic anhydrase inhibitors. De Simone G, Alterio V, Supuran CT. Expert Opin Drug Discov 8 793-810 (2013)
  7. Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy. Schönthal AH. Br J Cancer 97 1465-1468 (2007)
  8. Update on carbonic anhydrase inhibitors: a patent review (2008 - 2011). Aggarwal M, McKenna R. Expert Opin Ther Pat 22 903-915 (2012)
  9. Drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors. Supuran CT. Expert Opin Drug Metab Toxicol 12 423-431 (2016)
  10. Celecoxib analogs that lack COX-2 inhibitory function: preclinical development of novel anticancer drugs. Schönthal AH, Chen TC, Hofman FM, Louie SG, Petasis NA. Expert Opin Investig Drugs 17 197-208 (2008)
  11. 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)
  12. The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity. Jakubowski M, Szahidewicz-Krupska E, Doroszko A. Biomed Res Int 2018 4548353 (2018)
  13. The Expression of Carbonic Anhydrases II, IX and XII in Brain Tumors. Haapasalo J, Nordfors K, Haapasalo H, Parkkila S. Cancers (Basel) 12 E1723 (2020)
  14. Development of PET Radioligands Targeting COX-2 for Colorectal Cancer Staging, a Review of in vitro and Preclinical Imaging Studies. Dagallier C, Avry F, Touchefeu Y, Buron F, Routier S, Chérel M, Arlicot N. Front Med (Lausanne) 8 675209 (2021)

Articles citing this publication (33)

  1. N-Acylsulfonamides strongly inhibit human carbonic anhydrase isoenzymes I and II. Yıldırım A, Atmaca U, Keskin A, Topal M, Çelik M, Gülçin İ, Supuran CT. Bioorg Med Chem 23 2598-2605 (2015)
  2. Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT. Bioorg Med Chem 15 7229-7236 (2007)
  3. COX-Independent Mechanisms of Cancer Chemoprevention by Anti-Inflammatory Drugs. Gurpinar E, Grizzle WE, Piazza GA. Front Oncol 3 181 (2013)
  4. Insights towards sulfonamide drug specificity in α-carbonic anhydrases. Aggarwal M, Kondeti B, McKenna R. Bioorg Med Chem 21 1526-1533 (2013)
  5. A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects. Carta F, Di Cesare Mannelli L, Pinard M, Ghelardini C, Scozzafava A, McKenna R, Supuran CT. Bioorg Med Chem 23 1828-1840 (2015)
  6. Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide. Di Fiore A, Monti SM, Hilvo M, Parkkila S, Romano V, Scaloni A, Pedone C, Scozzafava A, Supuran CT, De Simone G. Proteins 74 164-175 (2009)
  7. SDTNBI: an integrated network and chemoinformatics tool for systematic prediction of drug-target interactions and drug repositioning. Wu Z, Cheng F, Li J, Li W, Liu G, Tang Y. Brief Bioinform 18 333-347 (2017)
  8. Carbonic anhydrases II and XII are up-regulated in osteoclast-like cells in advanced human atherosclerotic plaques-Tampere Vascular Study. Oksala N, Levula M, Pelto-Huikko M, Kytömäki L, Soini JT, Salenius J, Kähönen M, Karhunen PJ, Laaksonen R, Parkkila S, Lehtimäki T. Ann Med 42 360-370 (2010)
  9. 3-methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents. Abdellatif KR, Lamie PF, Omar HA. J Enzyme Inhib Med Chem 31 318-324 (2016)
  10. Carbonic anhydrase inhibitors. Aromatic/heterocyclic sulfonamides incorporating phenacetyl, pyridylacetyl and thienylacetyl tails act as potent inhibitors of human mitochondrial isoforms VA and VB. Güzel O, Innocenti A, Scozzafava A, Salman A, Supuran CT. Bioorg Med Chem 17 4894-4899 (2009)
  11. Probing the 'bipolar' nature of the carbonic anhydrase active site: aromatic sulfonamides containing 1,3-oxazol-5-yl moiety as picomolar inhibitors of cytosolic CA I and CA II isoforms. Krasavin M, Korsakov M, Dorogov M, Tuccinardi T, Dedeoglu N, Supuran CT. Eur J Med Chem 101 334-347 (2015)
  12. A class of carbonic anhydrase I - selective activators. Licsandru E, Tanc M, Kocsis I, Barboiu M, Supuran CT. J Enzyme Inhib Med Chem 32 37-46 (2017)
  13. Synthesis, molecular modeling, and biological evaluation of 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes. Yamali C, Gul HI, Ece A, Taslimi P, Gulcin I. Chem Biol Drug Des 91 854-866 (2018)
  14. N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors. Temperini C, Innocenti A, Scozzafava A, Supuran CT. Bioorg Med Chem Lett 16 4316-4320 (2006)
  15. 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)
  16. Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors. Güzel O, Innocenti A, Scozzafava A, Salman A, Supuran CT. Bioorg Med Chem Lett 19 3170-3173 (2009)
  17. Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV. Di Fiore A, Monti SM, Innocenti A, Winum JY, De Simone G, Supuran CT. Bioorg Med Chem Lett 20 3601-3605 (2010)
  18. The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme. Malebari AM, Ibrahim TS, Salem IM, Salama I, Khayyat AN, Mostafa SM, El-Sabbagh OI, Darwish KM. Pharmaceuticals (Basel) 13 E252 (2020)
  19. N-Acylbenzenesulfonamide Dihydro-1,3,4-oxadiazole Hybrids: Seeking Selectivity toward Carbonic Anhydrase Isoforms. Bianco G, Meleddu R, Distinto S, Cottiglia F, Gaspari M, Melis C, Corona A, Angius R, Angeli A, Taverna D, Alcaro S, Leitans J, Kazaks A, Tars K, Supuran CT, Maccioni E. ACS Med Chem Lett 8 792-796 (2017)
  20. Carbonic anhydrase inhibitors: the X-ray crystal structure of the adduct of N-hydroxysulfamide with isozyme II explains why this new zinc binding function is effective in the design of potent inhibitors. Temperini C, Winum JY, Montero JL, Scozzafava A, Supuran CT. Bioorg Med Chem Lett 17 2795-2801 (2007)
  21. Exploration of the binding mode of indanesulfonamides as selective inhibitors of human carbonic anhydrase type VII by targeting Lys 91. Thiry A, Masereel B, Dogné JM, Supuran CT, Wouters J, Michaux C. ChemMedChem 2 1273-1280 (2007)
  22. Spectroscopic study on the interaction of celecoxib with human carbonic anhydrase II: thermodynamic characterization of the binding process. Mehrabi M, Ghobadi S, Khodarahmi R. J Photochem Photobiol B 97 161-168 (2009)
  23. Intracellular Binding/Unbinding Kinetics of Approved Drugs to Carbonic Anhydrase II Observed by in-Cell NMR. Luchinat E, Barbieri L, Cremonini M, Nocentini A, Supuran CT, Banci L. ACS Chem Biol 15 2792-2800 (2020)
  24. Synthesis 4-[2-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-ethyl]-benzenesulfonamides with subnanomolar carbonic anhydrase II and XII inhibitory properties. Bozdag M, Alafeefy AM, Carta F, Ceruso M, Al-Tamimi AS, Al-Kahtani AA, Alasmary FAS, Supuran CT. Bioorg Med Chem 24 4100-4107 (2016)
  25. GCG100649, A Novel Cyclooxygenase-2 Inhibitor, Exhibits a Drug Disposition Profile in Healthy Volunteers Compatible With High Affinity to Carbonic Anhydrase-I/II: Preliminary Dose-Exposure Relationships to Define Clinical Development Strategies. Hirankarn S, Barrett JS, Alamuddin N, FitzGerald GA, Skarke C. Clin Pharmacol Drug Dev 2 379-386 (2013)
  26. Human carbonic anhydrase inhibitory profile of mono- and bis-sulfonamides synthesized via a direct sulfochlorination of 3- and 4-(hetero)arylisoxazol-5-amine scaffolds. Krasavin M, Korsakov M, Zvonaryova Z, Semyonychev E, Tuccinardi T, Kalinin S, Tanç M, Supuran CT. Bioorg Med Chem 25 1914-1925 (2017)
  27. Deuteration versus ethylation - strategies to improve the metabolic fate of an 18F-labeled celecoxib derivative. Laube M, Gassner C, Neuber C, Wodtke R, Ullrich M, Haase-Kohn C, Löser R, Köckerling M, Kopka K, Kniess T, Hey-Hawkins E, Pietzsch J. RSC Adv 10 38601-38611 (2020)
  28. Development of 3-(4-aminosulphonyl)-phenyl-2-mercapto-3H-quinazolin-4-ones as inhibitors of carbonic anhydrase isoforms involved in tumorigenesis and glaucoma. Alafeefy AM, Carta F, Ceruso M, Al-Tamimi AM, Al-Kahtani AA, Supuran CT. Bioorg Med Chem 24 1402-1407 (2016)
  29. Synthesis and biological evaluation of some N-arylpyrazoles and pyrazolo[3,4-d]pyridazines as anti-inflammatory agents. El-Sabbagh OI, Mostafa S, Abdel-Aziz HA, Ibrahim HS, Elaasser MM. Arch Pharm (Weinheim) 346 688-698 (2013)
  30. Treatment of sleep apnea with a combination of a carbonic anhydrase inhibitor and an aldosterone antagonist: a patent evaluation of CA2958110 and IN6616DEN2012. Angeli A, Supuran CT. Expert Opin Ther Pat 28 723-727 (2018)
  31. Mutation of active site residues Asn67 to Ile, Gln92 to Val and Leu204 to Ser in human carbonic anhydrase II: influences on the catalytic activity and affinity for inhibitors. Turkoglu S, Maresca A, Alper M, Kockar F, Işık S, Sinan S, Ozensoy O, Arslan O, Supuran CT. Bioorg Med Chem 20 2208-2213 (2012)
  32. Discovering isozyme-selective inhibitor scaffolds of human carbonic anhydrases using structural alignment and de novo drug design approaches. Xiang F, Xiang J, Fang Y, Zhang M, Li M. Chem Biol Drug Des 83 247-258 (2014)
  33. Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: synthesis, biological evaluations and modelling insights. Badawi WA, Rashed M, Nocentini A, Bonardi A, Abd-Alhaseeb MM, Al-Rashood ST, Veerakanellore GB, Majrashi TA, Elkaeed EB, Elgendy B, Gratteri P, Supuran CT, Eldehna WM, Elagawany M. J Enzyme Inhib Med Chem 38 2201407 (2023)


Quick links