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Interaction of Human Serum Albumin with Indomethacin: Spectroscopic and Molecular Modeling Studies

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Abstract

In this work, the interaction between indomethacin (IM) and human serum albumin (HSA) under simulative physiological conditions was investigated by the methods of fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular modeling. The experiment results showed that the fluorescence quenching of HSA by IM was a result of the formation of an IM–HSA complex and the corresponding association constants (K a) between IM and HSA at four different temperatures were determined according to the modified Stern–Volmer equation. The resulting thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures indicate that the hydrophobic force plays a major role for IM–HSA association, but hydrogen bonds also could not be excluded. A molecular modeling study further confirmed the binding mode and indicated that the binding of IM to HSA primarily takes place in sub-domain IIA (site I). The conformational investigation showed that the presence of IM decreased the α-helical content of HSA and induced slight unfolding of the polypeptides of protein, which confirmed that some microenvironmental and conformational changes occur for HSA molecules.

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References

  1. Colmenarejo, G.: In silico prediction of drug-binding strengths to human serum albumin. Med. Res. Rev. 23, 275–301 (2003)

    Article  CAS  Google Scholar 

  2. Zhang, Y.Z., Xiang, X., Mei, P., Dai, J., Zhang, L.L., Liu, Y.: Spectroscopic studies on the interaction of Congo Red with bovine serum albumin. Spectrochim. Acta, Part A, Mol. Biomol. Spectrosc. 72, 907–914 (2009)

    Article  Google Scholar 

  3. Carter, D.C., Ho, J.X.: Structure of serum albumin. Adv. Protein Chem. 45, 153–203 (1994)

    Article  CAS  Google Scholar 

  4. Zsila, F., Bikadi, Z., Simonyi, M.: Probing the binding of the flavonoid, quercetin to human serum albumin by circular dichroism, electronic absorption spectroscopy and molecular modelling methods. Biochem. Pharmacol. 65, 447–456 (2003)

    Article  CAS  Google Scholar 

  5. Qin, C., Xie, M.X., Liu, Y.: Characterization of the myricetin—human serum albumin complex by spectroscopic and molecular modeling approaches. Biomacromolecules 8, 2182–2189 (2007)

    Article  CAS  Google Scholar 

  6. Hu, Y.J., Liu, Y., Xiao, X.H.: Investigation of the interaction between berberine and human serum albumin. Biomacromolecules 10, 517–521 (2009)

    Article  CAS  Google Scholar 

  7. Bhattacharya, B., Nakka, S., Guruprasad, L., et al.: Interaction of bovine serum albumin with dipolar molecules: fluorescence and molecular docking studies. J. Phys. Chem. B 113, 2143–2150 (2009)

    Article  CAS  Google Scholar 

  8. Froehlich, E., Mandeville, J.S., Jennings, C.J., Sedaghat-Herati, R., Tajmir-Riahi, H.A.: Dendrimers bind human serum albumin. J. Phys. Chem. B 113, 6986–6993 (2009)

    Article  CAS  Google Scholar 

  9. Wojnarowska, Z., Adrjanowicz, K., Wlodarczyk, P., Kaminska, E., Kaminski, K., Grzybowska, K., Wrzalik, R., Paluch, M., Ngai, K.L.: Broadband dielectric relaxation study at ambient and elevated pressure of molecular dynamics of pharmaceutical: indomethacin. J. Phys. Chem. B 113, 12536–12545 (2009)

    Article  CAS  Google Scholar 

  10. Jain, A.K.: Solubilization of indomethacin using hydrotropes for aqueous injection. Eur. J. Pharm. Biopharm. 68, 701–714 (2008)

    Article  CAS  Google Scholar 

  11. Campanile, F., Giampietri, A., Grohmann, U., Belladonna, L.M., Fioretti, C.M., Puccetti, P.: Evidence for tumor necrosis factor a as mediator of toxicity of a cyclooxygenase inhibitor in Gram-negative sepsis. Eur. J. Pharmacol. 307, 191–199 (1996)

    Article  CAS  Google Scholar 

  12. Tsuboi, I., Tanaka, H., Nakao, M., Shichijo, S., Itoh, K.: Nonsteroidal anti-inflammatory drugs differentially regulate cytokine production in human lymphocytes: up-regulation of TNF, IFN-g and IL-2, in contrast to down-regulation of IL-6 production. Cytokine 7, 372–379 (1995)

    Article  CAS  Google Scholar 

  13. Parhar, R.S., Yagel, S., Lala, P.K.: PGE2-mediated immunosuppression by first trimester human decidual cells blocks activation of maternal leukocytes in the decidua with potential anti-trophoblast activity. Cell. Immunol. 120, 61–74 (1989)

    Article  CAS  Google Scholar 

  14. Kalgutkar, A.S., Marnett, A.B., Crews, B.C., Remmel, R.P., Marnett, L.J.: Ester and amide derivatives of the nonsteroidal antiinflammatory drug, Indomethacin, as selective cyclooxygenase-2 inhibitors. J. Med. Chem. 43, 2860–2870 (2000)

    Article  CAS  Google Scholar 

  15. Gridley, G., McLaughlin, J.K., Ekbom, A., Klareskog, L., Adami, H.O., Hacker, D.G., Hoover, R., Fraumeni, J.F. Jr.: Incidence of cancer among patients with rheumatoid arthritis. J. Natl. Cancer Inst. 85, 307–311 (1993)

    Article  CAS  Google Scholar 

  16. Hu, Y.J., Liu, Y., Zhang, L.X., Zhao, R.M., Qu, S.S.: Studies of interaction between colchicine and bovine serum albumin by fluorescence quenching method. J. Mol. Struct. 750, 174–178 (2005)

    Article  CAS  Google Scholar 

  17. Lakowicz, J.R.: Principles of Fluorescence Spectroscopy, 3rd edn., pp. 277–285. Springer, New York (2006)

    Book  Google Scholar 

  18. Zhang, H.X., Gao, S., Xiong, Z.J., Liu, S.P.: Fluorometric probing on the binding of hematoxylin to serum albumin. Mol. Biol. Rep. 36, 2299–2306 (2009)

    Article  CAS  Google Scholar 

  19. Zhang, H.X., Mei, P.: In vitro binding of furadan to bovine serum albumin. J. Solution Chem. 38, 351–361 (2009)

    Article  Google Scholar 

  20. Kathiravan, A., Renganathan, R., Anandan, S.: Interaction of colloidal AgTiO2 nanoparticles with bovine serum albumin. Polyhedron 28, 157–161 (2009)

    Article  CAS  Google Scholar 

  21. Ware, W.R.: Oxygen quenching of fluorescence in solution, an experimental study of the diffusion process. J. Phys. Chem. 66, 455–458 (1962)

    Article  CAS  Google Scholar 

  22. Kathiravan, A., Chandramohan, M., Renganathan, R., Sekar, S.: Spectroscopic studies on the interaction between phycocyanin and bovine serum albumin. J. Mol. Struct. 919, 210–214 (2009)

    Article  CAS  Google Scholar 

  23. Lehrer, S.S.: Solute perturbation of protein fluorescence. The quenching of the tryptophyl fluorescence of model compounds and of lysozyme by iodide ion. Biochemistry 10, 3254–3263 (1971)

    Article  CAS  Google Scholar 

  24. Leckband, D.: Measuring the forces that control protein interactions. Annu. Rev. Biophys. Biomol. Struct. 29, 1–26 (2000)

    Article  CAS  Google Scholar 

  25. Ross, D.P., Subramanian, S.: Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20, 3096–3102 (1981)

    Article  CAS  Google Scholar 

  26. Zhang, Y.Z., Zhang, N.X., Ren, A.Q., Zhang, J., Dai, J., Liu, Y.: Spectroscopic studies on the interaction of 2,4-dichlorophenol with bovine serum albumin. J. Solution Chem. 39, 495–510 (2010)

    Article  CAS  Google Scholar 

  27. Rahman, M.H., Maruyama, T., Okada, T., Yamasaki, K., Otagiri, M.: Study of interaction of carprofen and its enantiomers with human serum albumin—I: Mechanism of binding studied by dialysis and spectroscopic methods. Biochem. Pharmacol. 46, 1721–1731 (1993)

    Article  CAS  Google Scholar 

  28. Sjoholm, I., Ekman, B., Kober, A., Ljungstedt-Pahlman, I., Seiving, B., Sjodin, T.: Binding of drug to human serum albumin: XI. The specificity of three binding sites as studied with albumin immobilized in microparticles. Mol. Pharmacol. 16, 767–777 (1979)

    CAS  Google Scholar 

  29. Peters, T.: All about Albumin: Biochemistry, Genetics and Medical Applications. Academic Press, San Diego (1996)

    Google Scholar 

  30. Zhang, Y.Z., Zhou, B., Liu, Y.X., Zhou, C.X., Ding, X.L., Liu, Y.: Fluorescence study on the interaction of bovine serum albumin with p-aminoazobenzene. J. Fluoresc. 18, 109–118 (2008)

    Article  CAS  Google Scholar 

  31. Carter, D.C., He, X.M., Munson, S.H., Twigg, P.D., Gernert, K.M., Broom, M.B., Miller, T.Y.: Three-dimensional structure of human serum albumin. Science 244, 1195–1196 (1989)

    Article  CAS  Google Scholar 

  32. Li, Y.S., Ge, Y.S., Zhang, Y., Zhang, A.Q., Sun, S.F., Jiang, F.L., Liu, Y.: Interaction of coomassie brilliant blue G250 with human serum albumin: probing of the binding mechanism and binding site by spectroscopic and molecular modeling methods. J. Mol. Struct. 968, 24–31 (2010)

    Article  CAS  Google Scholar 

  33. He, X.M., Carter, D.C.: Atomic structure and chemistry of human serum albumin. Nature 358, 209–215 (1992)

    Article  CAS  Google Scholar 

  34. Sahoo, B.K., Ghosh, K.S., Dasgupta, S.: Investigating the binding of curcumin derivatives to bovine serum albumin. Biophys. Chem. 132, 81–88 (2008)

    Article  CAS  Google Scholar 

  35. Liu, J.Q., Tian, J.N., Tian, X., Hu, Z.D., Chen, X.G.: Interaction of isofraxidin with human serum albumin. Bioorg. Med. Chem. 12, 469–474 (2004)

    Article  CAS  Google Scholar 

  36. Sreerama, N., Woody, R.W.: A self-consistent method for the analysis of protein secondary structure from circular dichroism. Anal. Biochem. 209, 32–44 (1993)

    Article  CAS  Google Scholar 

  37. Whitmore, L., Wallace, B.A.: DICHROWEB, an online server for protein secondary structure analyses from circular dichroism spectroscopic data. Nucleic Acids Res. 32, 668–673 (2004)

    Article  Google Scholar 

  38. Cui, F.L., Fan, J., Li, J.P., Hu, Z.D.: Interactions between 1-benzoyl-4-p-chlorophenyl thiosemicarbazide and serum albumin: investigation by fluorescence spectroscopy. Bioorg. Med. Chem. 12, 151–157 (2004)

    Article  CAS  Google Scholar 

  39. Li, X.Y.: Interaction of metronidazole with bovine serum albumin by using fluorescence and resonance light scattering spectra. Acta Phys.-Chim. Sin. 23, 262–267 (2007)

    CAS  Google Scholar 

  40. Xiao, Q., Huang, S., Liu, Y., Tian, F.F., Zhu, J.C.: Thermodynamics, conformation and active sites of the binding of Zn–Nd hetero-bimetallic Schiff base to bovine serum albumin. J. Fluoresc. 19, 317–326 (2009)

    Article  CAS  Google Scholar 

  41. Tian, J.N., Liu, J.Q., Hu, Z.D., Chen, X.G.: Interaction of wogonin with bovine serum albumin. Bioorg. Med. Chem. 13, 4124–4129 (2005)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the financial support from the National Natural Science Foundation of China (Grant No. 20921062), Research Program of Hubei Province Department of Education (D20101302) and the National Innovation Experiment Program for University Students (101048902).

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Correspondence to Ye-Zhong Zhang or Yi Liu.

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Zhang, J., Sun, HH., Zhang, YZ. et al. Interaction of Human Serum Albumin with Indomethacin: Spectroscopic and Molecular Modeling Studies. J Solution Chem 41, 422–435 (2012). https://doi.org/10.1007/s10953-012-9809-4

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  • DOI: https://doi.org/10.1007/s10953-012-9809-4

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