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Multiple Spectroscopic, Docking and Cytotoxic Study of a Synthesized 2,2′ Bipyridin Phenyl Isopentylglycin Pt(II) Nitrate Complex: Human Serum Albumin and Breast Cancer Cell Line of MDA-MB231 as Targets

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Abstract

In the present study, the biological activities of a new synthesized Pt(II)-complex, 2,2′ bipyridinphenyl isopentylglycin Pt(II) nitrate was investigated via its interaction with the most important blood carrier protein of human serum albumin (HSA), using fluorescence and Far-UV circular dichroism (CD) spectroscopic techniques and also molecular docking. Moreover, cytotoxicity activity of the complex was studied against breast cancer cell line of MDA MB231 using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The Pt(II)-complex has a strong ability to quench the intrinsic fluorescence of HSA through a static quenching mechanism. According fluorescence quenching data, the binding parameters of the interaction were calculated and showed that hydrophobic interaction has an important role. The molecular docking results in coherent with fluorescence measurements illustrated that Pt(II) complex can bind to HSA at one position that located in the hydrophobic cavity of groove between drug site I and II. Also, experimental data on driving force in binding site was confirmed whereas theoretical results demonstrated Pt(II) complexinteract to HSA by hydrophobic interaction. Far-UV-CD results showed that Pt(II)-complex induced an increasing in the content of α-helical structure of the protein and stabilized it. Also, MTT assay represented growth inhibitory effect of the complex toward the breast cancer cell line.

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References

  1. Wang YQ, Zhang HM, Zhang GC, Tao WH, Tang SH (2007) Binding of brucine to human serum albumin. J Mol Struct 830:40–45

    Article  CAS  Google Scholar 

  2. Meloun B, Morávek L, Kotska V (1975) Complete amino acid sequence of human serum albumin. FEBS Lett 58:134–137

    Article  PubMed  CAS  Google Scholar 

  3. Trynda-Lemiesz L, Kozøowski H, Keppler BK (1999) Effect of cis-, trans-diamminedichloroplatinum(II) and DBP on human serum albumin. J Inorg Biochem 77:141–146

    Article  PubMed  CAS  Google Scholar 

  4. Soskic M, Magnus V (2007) Binding of ring-substituted indole-3-acetic acids to human serum albumin. BioorgMed Chem 15:4595–4600

    Article  CAS  Google Scholar 

  5. Kratz F (2008) Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J Control Rel 132:171–183

    Article  CAS  Google Scholar 

  6. Ascenzi P, Fasano M (2010) Allostery in a monomeric protein: the case of human serum albumin. Biophys Chem 148:16–22

    Article  PubMed  CAS  Google Scholar 

  7. Zunszain PA, Ghuman J, Komatsu T, Tsuchida E (2003) The general structure of Albumin is characterized by several long β (beta) sheets. BMC Struct Biol 3:6–14

    Article  PubMed  PubMed Central  Google Scholar 

  8. Honore B (1990) Conformational changes in human serum albumin induced by ligand binding. PharmacolToxicol 66:7–26

    Google Scholar 

  9. Cheng FQ, Wang YP, Li ZP, Dong C (2006) Fluorescence study on the interaction of human serum albumin with bromsulphalein. SpectrochimActa Part A 65:1144–1147

    Article  CAS  Google Scholar 

  10. Rezaei-Tavirani M, Moghaddamnia SH, Ranjbar B, Amani M, Marashi SA (2006) Conformational study of human serum albumin in pre-denaturation temperatures by differential scanning calorimetry, circular dichroism and UV spectroscopy. J Biochem Mol Biol 39:530–536

    PubMed  CAS  Google Scholar 

  11. Trynda-Lemiesz L, Łuczkowski M (2004) Human serum albumin: spectroscopic studies of the paclitaxel binding and proximity relationships with cisplatin and adriamycin. J Inorg Biochem 98:1851–1856

    Article  PubMed  CAS  Google Scholar 

  12. Subramanyam R, Gollapudi A, Bonigala P, Chinnaboina M, Amooru DG (2009) Betulinic acid binding to human serum albumin: a study of protein conformation and binding affinity. J Photochem Photobiol B Biol 94:8–12

    Article  CAS  Google Scholar 

  13. Cicheics RH, Kouzi SA (2004) Chemistry, biological activity and chemotherapeutic potential of betulinic acid for the preventation and treatment of cancer and HIV infection. Med Chem Res Rev 24:90–114

    Article  CAS  Google Scholar 

  14. Almeida GM, Duarte TL, Steward WP, Jones GDD (2006) Detection of oxaliplatin-induced DNA crosslinks in vitro and in cancer patients using the alkaline comet assay. DNA Repair 5:219–225

    Article  PubMed  CAS  Google Scholar 

  15. Giovagnini L, Marzano C, Bettio F, Fregona D (2005) Chemical and biological profiles of novel copper(II) complexes containing S-Donor ligands for the treatmentof cancer. J Inorg Biochem 99:2139

    Article  PubMed  CAS  Google Scholar 

  16. Zhang Q, Zhong W, Xing B, Tang W, Chen Y (1998) Binding properties and stoichiometries of a palladium(II) complex to metallothioneinsin vivo and in vitro. J Inorg Biochem 72:195–200

    Article  PubMed  CAS  Google Scholar 

  17. Mansouri-Torshizi H, I-Moghaddam M, Divsalar A, Saboury AA (2009) DiiminePlatinum(II) and Palladium(II) complexes of dithiocarbamate derivative as potential antitumor agents: synthesis, characterization, cytotoxicity, and detail DNAbinding studies. J Biomol Struct Dyn 26:575–586

    Article  PubMed  CAS  Google Scholar 

  18. Divsalar A, Saboury AA, Mansoori-Torshizi H, Ahmad F (2010) Design, synthesis, and biological evaluation of a new Palladium(II) complex: Beta-lactoglobulin and K562 as targets. J Phys Chem B 114:3639–3647

    Article  PubMed  CAS  Google Scholar 

  19. Mansouri-Torshizi H, Saeidifar M, Khosravi F, Divsalar A, Saboury AA, YekkeGhasemi Z (2011) DNA-binding and thermodynamic parameters, structure and cytotoxicity of newly designed Platinum(II) and Palladium(II) anti-tumor complexes. Bull Korean Chem Soc 32:947–955

    Article  CAS  Google Scholar 

  20. Divsalar A, Saboury AA, Ahadi L, Zemanatiyar E, Mansouri- Torshizi H, Ajloo D et al (2011) Biological evaluation and interaction of a newly designed anti-cancer Pd(II) complex and human serum albumin. J Biomol Struct Dyn 29(2):283–296

    Article  PubMed  CAS  Google Scholar 

  21. Divsalar A, Razmi M, Saboury AA, Mansouri-Torshizi H, Ahmad F (2015) Biological evaluation of a new synthesized Pt(II) complex by cytotoxic and spectroscopic studies. Cell BiochemBiophys 71:1415–1424

    Article  CAS  Google Scholar 

  22. Marzano C, Fregona D, Baccichetti F, Trevisan A, Giovagnini L, Bordin F (2002) Cytotoxicity and DNA damage induced by a new Platinum(II) complex with pyridine and dithiocarbamate. Chem Biol Interact 140:215–229

    Article  PubMed  CAS  Google Scholar 

  23. Divsalar A, Bagheri MJ, Saboury AA, Mansoori- Torshizi H, Amani M (2009) Investigation on the interaction of new designed anti-cancer Pd(II) complexes with different aliphatic tails and Human serum albumin. JPhys Chem B 113:14035–14042

    Article  CAS  Google Scholar 

  24. Yang JT, Wu CSC, Martinez HM (1981) Direct determination of absolute circular dichroism data and calibration of commercial instrument. AnalChem 53:778

    Google Scholar 

  25. Manavalan P, Johnson CJR (1987) Variable selection method improves the prediction of protein secondary structure from circular dichroism spectra. AnalBiochem 167:76–85

    CAS  Google Scholar 

  26. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) J Comput Chem 30:2785–2791

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. HyperChem8.0.6, Molecular visualization and simulation program package, Hypercube, Inc., Gainesville

  28. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Zakrzewski VG, Montgomery JA Jr, Stratmann RE, Burant JC, Dapprich S, Millam JM, Daniels AD, Kudin KN, Strain MC, Farkas O, Tomasi J, Barone V, Cossi M, Cammi R, Mennucci B, Pomelli C, Adamo C, Clifford S, Ochterski J, Petersson GA, Ayala PY, Cui Q, Morokuma K, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Cioslowski J, Ortiz JV, Baboul AG, StefanovG BB. Liu A, Liashenko P, Piskorz I, Komaromi R, Gomperts RL, Martin DJ, Fox T, Keith MA, Al-Laham CY, Peng A, Nanayakkara C, Gonzalez M, Challacombe PMW, Gill B, Johnson W, Chen MW, Wong JL, Andres C, Gonzalez M, Head-Gordon, ES. Replogle, and Pople JA, 1998. Gaussian 98, Revision A.7, Gaussian, Inc., Pittsburgh, PA

  29. Petitpas I, Bhattacharya AA (2001) Sue Twine, Malcolm East, Stephen Curry, crystal structure analysis of warfarin binding to human serum Albumin: ANATOMY OF DRUG SITE I. J Biol Chem 276:22804–22809

    Article  PubMed  CAS  Google Scholar 

  30. Ghalandari B, Divsalar A, Eslami-Moghadam M, Saboury AA, Haertlé T, Amanlou M, Parivar K, Probing of the Interaction Between β-Lactoglobulin and the Anticancer Drug Oxaliplatin., ApplBiochemBiotechnol (2015) 175:974–987

  31. Ghalandari B, Divsalar A, Saboury AA, Haertlé T, Parivar K, Bazl R, Eslami-Moghadam M, Amanlou M (2014) Spectroscopic and theoretical investigation of oxali-palladium interactions with β-lactoglobulin. Spectrochim Acta Part A: Mol Biomol Spectrosc 118:1038–1046

    Article  CAS  Google Scholar 

  32. Wolber G, Dornhofer AA, Langer T (2006) Efficient overlay of small organic molecules using 3D pharmacophores. J Comput Aided Mol Des 20:773–788

    Article  PubMed  CAS  Google Scholar 

  33. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function. J Comput Chem 19:1639–1662

    Article  CAS  Google Scholar 

  34. Sanner MF (1999) Python: a programming language for software integration and development. J Mol Graph Model 17:57–61

    PubMed  CAS  Google Scholar 

  35. Humphrey W, Dalke A, Schulten K (1996) VMD- Visual Molecular Dynamics. J Molec Graphics 14.1:33–38

    Article  Google Scholar 

  36. Laskowski RA, Swindells MB (2011) LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 51:2778–2786

    Article  PubMed  CAS  Google Scholar 

  37. Divsalar A, Saboury AA, Yousefi R, Moosavi-Movahedi AA, Mansoori-Torshizi H (2006) Spectroscopic and cytotoxic studies of the Novel designed Pd(II) complexes: beta-lactoglobulin and K562 as the targets. Int J Biol Macromol 40:381–386

    Article  PubMed  CAS  Google Scholar 

  38. Shpigelman A, Livney YD (2010) Thermally-induced protein polyphenol co-assemblies: beta lactoglobulin-based nanocomplexes as protective nanovehicles for EGCG. Food Hydrocolloids 24:735–743

    Article  CAS  Google Scholar 

  39. Lakowicz JR (1999) Principles of Fluorescence Spectroscopy, 2nd edn. Kluwer Academic Publishers/Plenum Press, New York

  40. Ambrosetti R, Bianchini R, Fischella S, Fichera M, Zandomeneghi M (1996) Resolution of the absorbance and CD spectra and formation constants of the complexes between human serum albumin and methyl orange. ChemEur J 2:149–156

    CAS  Google Scholar 

  41. Geddes CD, Lakowicz JR (2005) Reviews in fluorescence. Springer, New York, pp 199–222

    Google Scholar 

  42. Zhang Y, Qi Z, Zheng D, Li C (2009) Interactions of Chromium (III) and Chromium (VI) with bovine serum albumin studied by UV spectroscopy, circular dichroism, and fluorimetry. Biol Trace Elem Res 130:172–184

    Article  PubMed  CAS  Google Scholar 

  43. Cui F, Zhang Q, Yan Y, Yao X, Qu G, Lu Y (2008) Study of characterization and application on the binding between 5-iodouridine with HSA by spectroscopic and modeling. Carbohyd Polym 73:464–472

    Article  CAS  Google Scholar 

  44. Lakowicz JR (1999). In: Dewey TG (ed) Principles of fluorescence spectroscopy, 2nd edn. Plenum Press, New York

  45. Liu XF, Xia YM, Fang YJ (2005) Effect of metal ions on the interaction between bovine serum albumin and berberine chloride extracted from a traditional Chinese herb coptischinensisfranch between. J Inorg Biochem 99:1449–1457

    Article  PubMed  CAS  Google Scholar 

  46. Timasheff SN (1972) Thermodynamic of protein interactions. In: Peeters H (ed) Proteins of biological fluids. Pergamon Press, Oxford

    Google Scholar 

  47. Rahman MH, Maruyama T, Okada T, Masaki KY, Otagiri M (1993) 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

    Article  PubMed  CAS  Google Scholar 

  48. Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions forced contributing to stability. Biochemistry 20:3096–3102

    Article  PubMed  CAS  Google Scholar 

  49. Yamamoto T, Yokoyama M, Opanasopit P, Hayama A, Kawano K, Maitani Y (2007) What are determining factors for stable drug incorporation into polymeric micelle carriers? Consideration on physical and chemical characters of the micelle inner core. J Controlled Release 123:11–18

    Article  CAS  Google Scholar 

  50. Wallace BA, Lees JG, Orry AJW, Lobley A, Janes RW (2003) Analyses of circular dichroism spectra of membrane proteins. Protein Sci 12:875–884

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Wang K, Lu JF, Li RC (1996) The events that occur when cisplatin encounters cells. Coord Chem Rev 151:53–88

    Article  CAS  Google Scholar 

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Acknowledgements

The financial support of the Research Council of the Kharazmi University is highly appreciated.

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Authors and Affiliations

  1. Department of Cell & Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Sara Nourizadeh, Adeleh Divsalar & Mina Fekri

  2. Department of Medical Nanotechnology, Science and Research Branch Islamic Azad University, Tehran, Iran

    Behafarid Ghalandari

  3. Chemistry and Engineer Chemistry Research Center, Tehran, Iran

    Mahbubeh Eslami-Moghadam

  4. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    Ali Akbar Saboury

  5. Department of Cell & Molecular Biology, Faculity of Biological Sciences, Shahed University, Tehran, Iran

    Saba Abbasi

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  1. Sara Nourizadeh
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Correspondence to Adeleh Divsalar.

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Nourizadeh, S., Divsalar, A., Fekri, M. et al. Multiple Spectroscopic, Docking and Cytotoxic Study of a Synthesized 2,2′ Bipyridin Phenyl Isopentylglycin Pt(II) Nitrate Complex: Human Serum Albumin and Breast Cancer Cell Line of MDA-MB231 as Targets. J Fluoresc 28, 551–559 (2018). https://doi.org/10.1007/s10895-018-2216-5

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