QM Study on the Mechanism of Carbonic Anhydrase II Inhibition with Glycosylcoumarin as Non-Zinc Mediated Inhibitors from Thermodynamic View Point
DOI:
https://doi.org/10.6000/1929-5634.2017.06.04.4Keywords:
Carbonic Anhydrase, glycosylcoumarin, inhibition mechanism, Density functional theory, explicit solvent methodAbstract
Carbonic anhydrase is an enzyme which has the zinc as the metallic part of it. This enzyme catalyzes the reversible reaction of turning carbon dioxide into bicarbonate. In this research the mechanism of inhibition a new class of inhibitor of this enzyme, glycosyl coumarin has been modeled using the density functional theory (DFT). First, the most constant confirmer of this four coumarin sugar derivatives which includes galactose, mannose, ribose and glucose has been selected and then they had been interacted as inhibitor with CA (II) enzyme’s active site. In further for showing the effect of sugar in these molecules, coumarin itself had been chosen as inhibitor and the inhibitory effect is surveyed. All calculations have been done by density functional theory in level of B3LYP with basic set 6-31G* and with Minnesota function M06 with basic set 6-31+G*. Thermodynamic functions like enthalpy of formation, entropy of formation and Gibbs free energy for CA-inhibitor have been computed. The results indicate that the reaction among these groups of inhibitors and Carbonic anhydrase is not of the type of direct and syndetic but the enzyme is deactivated with space effect and addition to this, the computed thermodynamic functions show that although this coumarin sugar derives have deterrence in the range of micro molar but, coumarin without sugar is a stronger deterrence for CA II. Finally, the interaction between the most constant confirmer (galactose coumarin) is surveyed as the best deterrence using the explicit solvent method.
References
Supuran CT. Carbonic anhydrase inhibition with natural products: novel chemotypes and inhibition mechanisms. Mol Divers 2011; 15: 305-16. https://doi.org/10.1007/s11030-010-9271-4 DOI: https://doi.org/10.1007/s11030-010-9271-4
Supuran CT. Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat Rev Drug Discov 2008; 7: 168-81. https://doi.org/10.1038/nrd2467 DOI: https://doi.org/10.1038/nrd2467
Xu Y, Feng L, Jeffrey PD, Shi Y, Morel FM. Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms. Nat Hum Behav 2008; 452: 56-61. https://doi.org/10.1038/nature06636 DOI: https://doi.org/10.1038/nature06636
Moya A, Tambutté S, Bertucci A, et al. Carbonic anhydrase in the scleractinian coral Stylophora pistillata characterization, localization, and role in biomineralization. J Biol Chem 2008; 283: 25475-84. https://doi.org/10.1074/jbc.M804726200 DOI: https://doi.org/10.1074/jbc.M804726200
Nishimori I, Onishi S, Takeuchi H, Supuran CT. The α and β classes carbonic anhydrases from Helicobacter pylori as novel drug targets. Curr Pharm Des 2008; 14: 622-30. https://doi.org/10.2174/138161208783877875 DOI: https://doi.org/10.2174/138161208783877875
Švastová E, Hulı́ková A, Rafajová M, et al. Hypoxia activates the capacity of tumor‐associated carbonic anhydrase IX to acidify extracellular pH. FEBS Lett 2004; 577: 439-45. https://doi.org/10.1016/j.febslet.2004.10.043 DOI: https://doi.org/10.1016/j.febslet.2004.10.043
Ebbesen P, Pettersen EO, Gorr TA, et al. Taking advantage of tumor cell adaptations to hypoxia for developing new tumor markers and treatment strategies. J Enzyme Inhib Med Chem 2009; 24: 1-39. https://doi.org/10.1080/14756360902784425 DOI: https://doi.org/10.1080/14756360902784425
Supuran CT, Scozzafava A, Casini A. Carbonic anhydrase inhibitors. Med Res Rev 2003; 23: 146-89. https://doi.org/10.1002/med.10025 DOI: https://doi.org/10.1002/med.10025
Supuran CT. Carbonic anhydrases-an overview. Curr Pharm Des 2008; 14: 603-14. https://doi.org/10.2174/138161208783877884 DOI: https://doi.org/10.2174/138161208783877884
Rowlett RS. Structure and catalytic mechanism of the β-carbonic anhydrases. Biochim Biophys Acta 2010; 1804: 362-73. https://doi.org/10.1016/j.bbapap.2009.08.002 DOI: https://doi.org/10.1016/j.bbapap.2009.08.002
Zimmerman SA, Ferry JG, Supuran CT. Inhibition of the archaeal β-class (Cab) and γ-class (Cam) carbonic anhydrases. Curr Top Med Chem 2007; 7: 901-8. https://doi.org/10.2174/156802607780636753 DOI: https://doi.org/10.2174/156802607780636753
Monti SM, Supuran CT, De Simone G. Anticancer carbonic anhydrase inhibitors: a patent review (2008–2013). Expert Opin Ther Pat 2013; 23: 737-49. https://doi.org/10.1517/13543776.2013.798648 DOI: https://doi.org/10.1517/13543776.2013.798648
Venters RA, Farmer II BT, Fierke CA, Spicer LD. Characterizing the use of perdeuteration in NMR studies of large proteins: 13 C, 15 N and 1 H assignments of human carbonic anhydrase II. J Mol Biol 1996; 264: 1101-16. https://doi.org/10.1006/jmbi.1996.0699 DOI: https://doi.org/10.1006/jmbi.1996.0699
Supuran CT. Carbonic anhydrase inhibitors: an editorial. Expert Opin Ther Pat 2013; 23: 677-9. https://doi.org/10.1517/13543776.2013.778246 DOI: https://doi.org/10.1517/13543776.2013.778246
Supuran CT, Maresca A, Gregáň F, Remko M. Three new aromatic sulfonamide inhibitors of carbonic anhydrases I, II, IV and XII. J Enzyme Inhib Med Chem 2013; 28: 289-93. https://doi.org/10.3109/14756366.2011.649269 DOI: https://doi.org/10.3109/14756366.2011.649269
Neri D, Supuran CT. Interfering with pH regulation in tumours as a therapeutic strategy. Nat Rev Drug Discov 2011; 10: 767-77. https://doi.org/10.1038/nrd3554 DOI: https://doi.org/10.1038/nrd3554
Thiry A, Dogne JM, Masereel B, Supuran CT. Targeting tumor-associated carbonic anhydrase IX in cancer therapy. Trends Pharmacol Sci 2006; 27: 566-73. https://doi.org/10.1016/j.tips.2006.09.002 DOI: https://doi.org/10.1016/j.tips.2006.09.002
Supuran CT. Carbonic anhydrase inhibitors and activators for novel therapeutic applications. Future Med Chem 2011; 3: 1165-80. https://doi.org/10.4155/fmc.11.69 DOI: https://doi.org/10.4155/fmc.11.69
Maresca A, Temperini C, Vu H, et al. Non-Zinc Mediated Inhibition of Carbonic Anhydrases: Coumarins Are a New Class of Suicide Inhibitors#. J Am Chem Soc 2009; 131: 3057-62. https://doi.org/10.1021/ja809683v DOI: https://doi.org/10.1021/ja809683v
Maresca A, Temperini C, Pochet L, Masereel B, Scozzafava A, Supuran CT. Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. J Med Chem 2009; 53: 335-44. https://doi.org/10.1021/jm901287j DOI: https://doi.org/10.1021/jm901287j
(a) Maresca A, Supuran CT. Coumarins incorporating hydroxy-and chloro-moieties selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones I and II. Bioorg Med Chem Lett 2010; 20: 4511-4. https://doi.org/10.1016/j.bmcl.2010.06.040 DOI: https://doi.org/10.1016/j.bmcl.2010.06.040
(b) Maresca A, Scozzafava A, Supuran CT. 7, 8-Disubstituted-but not 6, 7-disubstituted coumarins selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones I and II in the low nanomolar/subnanomolar range. Bioorg Med Chem Lett 2010; 20: 7255-8.https://doi.org/10.1016/j.bmcl.2010.10.094 DOI: https://doi.org/10.1016/j.bmcl.2010.10.094
Bonneau A, Maresca A, Winum JY, Supuran CT. Metronidazole-coumarin conjugates and 3-cyano-7-hydroxy-coumarin act as isoform-selective carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem 2013; 28: 397-401. https://doi.org/10.3109/14756366.2011.650692 DOI: https://doi.org/10.3109/14756366.2011.650692
Touisni N, Maresca A, McDonald PC, et al. Glycosyl coumarin carbonic anhydrase IX and XII inhibitors strongly attenuate the growth of primary breast tumors. J Med Chem 2011; 54: 8271-7. https://doi.org/10.1021/jm200983e DOI: https://doi.org/10.1021/jm200983e
Wagner J, Avvaru BS, Robbins AH, Scozzafava A, Supuran CT, McKenna R. Coumarinyl-substituted sulfonamides strongly inhibit several human carbonic anhydrase isoforms: solution and crystallographic investigations. Bioorg Med Chem 2010; 18: 4873-8. https://doi.org/10.1016/j.bmc.2010.06.028 DOI: https://doi.org/10.1016/j.bmc.2010.06.028
Spicer SS, Ge ZH, Tashian RE, Hazen‐Martin DJ, Schulte BA. Comparative distribution of carbonic anhydrase isozymes III and II in rodent tissues. Am J Anat 1990; 187: 55-64. https://doi.org/10.1002/aja.1001870107 DOI: https://doi.org/10.1002/aja.1001870107
MJ Frisch, GW Trucks, HB Schlegel, GE Scuseria, et al. Gaussian. Inc., Wallingford CT. 2009.
Dennington RD, Keith TA, Millam JM. GaussView 5.0. 8. Gaussian Inc. 2008.
Parr RG, Yang W. Density Functional Theory of Atoms and Molecules Oxford Univ. Press, New York. 1989.
Becke AD. Density‐functional thermochemistry. III. The role of exact exchange. J Chem Phys 1993; 98: 5648-52. https://doi.org/10.1063/1.464913 DOI: https://doi.org/10.1063/1.464913
Zhao Y, Truhlar DG. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 2008; 120: 215-41. https://doi.org/10.1007/s00214-007-0310-x DOI: https://doi.org/10.1007/s00214-007-0310-x
Navarrete M, Rangel C, Corchado JC, Espinosa-Garcia J. Trapping of the OH radical by α-tocopherol: a theoretical study. J Phys Chem A 2005; 109: 4777-84. https://doi.org/10.1021/jp050717e DOI: https://doi.org/10.1021/jp050717e
Chandra AK, Uchimaru T. The OH bond dissociation energies of substituted phenols and proton affinities of substituted phenoxide ions: A DFT study. Int J Mol Sci 2002; 3: 407-22. https://doi.org/10.3390/i3040407 DOI: https://doi.org/10.3390/i3040407
Zhang HY, Ji HF. S–H proton dissociation enthalpies of thiophenolic cation radicals: a DFT study. J Mol Struct 2003; 663: 167-74. https://doi.org/10.1016/j.theochem.2003.08.124 DOI: https://doi.org/10.1016/j.theochem.2003.08.124
Downloads
Published
How to Cite
Issue
Section
License
Policy for Journals/Articles with Open Access
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work
Policy for Journals / Manuscript with Paid Access
Authors who publish with this journal agree to the following terms:
- Publisher retain copyright .
- Authors are permitted and encouraged to post links to their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work .
