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Design, synthesis and in vitro bioactivity of mixed ligand Ru(II) complexes bearing the fluoroquinolone antibacterial agents

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Abstract

Mixed ligand Ru(II) phenanthroline complexes of the type [Ru(1,10-phen)2Flq]ClO4 (RPFlq-1-3) and “piano-stool”-type Ru(II) arene complexes [Ru(η6-p-cymene)Cl(Flq)] (RAFlq-1-3), where Flq = fluoroquinolone, have been synthesized, characterized and studied for their anticancer potential. DFT calculations were in line with the proposed structures, wherein the fluoroquinolones are coordinated to the metal through the ring carbonyl and one of the carboxylic oxygen atoms in a bidentate fashion. Binding efficacies of the synthesized complexes with bovine serum albumin (BSA) and CT-DNA were studied spectroscopically, and it has been established that the arene complexes, though have moderate binding propensities to CT-DNA (Kb = 0.8–1.7 × 103 M−1), have 102–103-fold better binding efficacies toward BSA (Ka = 3.2 × 105–2.1 × 106 M−1) due to the presence of the hydrophobic arene moiety. These results further prompted a study in their in vitro cytotoxicity assay on A-549 non-small cell lung cancer and MCF7 breast cancer cell lines. Furthermore, gene expression studies on BAX and BCL-2 genes and FACS analysis confirmed apoptosis as the mode of cell death.

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References

  1. Allardyce CS, Dyson PJ (2001) Platinum Metals Rev. 45:62

    CAS  Google Scholar 

  2. Lentzen O, Moucheron C, Kirsch-De Mesmaeker A (2005) Metallotherapeutic drugs & metal-based diagnostic agents. Wiley, West Sussex, pp 359–378

    Google Scholar 

  3. Schluga P (2006) Dalton Trans 14:1796

    Google Scholar 

  4. Pongratz M, Schluga P, Jakupec M, Arion VB, Hartinger C, Allmaier G, Keppler BK (2004) J Anal At Spectrom 19:46

    CAS  Google Scholar 

  5. Zanzi I, Srivastava SC, Meinken GE, Robeson W, Mausner LF, Fairchild RG, Margouleff D (1989) Nucl Med Biol 16:397

    CAS  Google Scholar 

  6. Srivastava SC (1996) Semin Nucl Med 26:119

    CAS  PubMed  Google Scholar 

  7. Zeng L, Gupta P, Chen Y, Wang E, Ji L, Chao H, Zhe-Sheng C (2017) Chem Soc Rev 46:5771

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Barcelo M, Garcia A, Terroon A, Molins E, Prieto MJ, Moreno V, Martinez J, Llado V, Lopez I, Gutierrez A, Escriba PV (2007) J Inorg Biochem 101:649

    Google Scholar 

  9. Hartinger CG, Dyson PJ (2009) Chem Soc Rev 38:391

    CAS  PubMed  Google Scholar 

  10. Y.Yaw Kai, Chem. Comm. 2005, 38, 4764

  11. Soni K (2012) Indo Glob J Pharm Sci 2:43

    CAS  Google Scholar 

  12. Ronald AR, Low DE (2003) Fluoroquinolone antibiotics. Birkhäuser, Basel, p 250

    Google Scholar 

  13. Kwok Y, Sun D, Clement JJ, Hurley LH (1999) Anti-Cancer Drug Des 14:443

    CAS  Google Scholar 

  14. Yu H, Kwok Y, Hurley LH, Kerwin SM (2000) Biochemistry 39:10236

    CAS  PubMed  Google Scholar 

  15. Rinky S, Ravirajsinh NJ, Menaka CT, Ranjitsinh VD, Debjani C (2012) Transit Met Chem 37:541

    Google Scholar 

  16. Ramadevi P, Rinky S, Sarmita SJ, Ranjitsinh VD, Debjani C (2017) J Organomet Chem 833:80

    CAS  Google Scholar 

  17. Ramadevi P, Rinky S, Sarmita SJ, Ranjitsinh VD, Debjani C (2015) J Photochem Photobio AChem 305:1

    CAS  Google Scholar 

  18. Sullivan BP, Salmon DJ, Meyer TJ (1978) Inorg Chem 17:3334

    CAS  Google Scholar 

  19. Bennett MA, Smith AK (1974) J Chem Soc Dalton Trans (2):233

  20. Bennett MA, Huang TN, Matheson TW, Smith AK (1983) Inorg Synth 21:74

    Google Scholar 

  21. Neese F (2012) Wiley Interdiscip Rev Comput Mol Sci 2:73

    CAS  Google Scholar 

  22. Perdew JP (1986) Phys Rev B 33:8822

    CAS  Google Scholar 

  23. Becke AD (1988) Phys Rev A 38:3098

    CAS  Google Scholar 

  24. Becke AD (1988) Phys Rev A 38:3098

    CAS  Google Scholar 

  25. Weigend F, Ahlrichs R (2005) Phys Chem Chem Phys 7:3297

    CAS  PubMed  Google Scholar 

  26. Weigend F (2006) Phys Chem Chem Phys 8:1057

    CAS  PubMed  Google Scholar 

  27. Andrae D, Haeussermann U, Dolg M, Stoll H, Preuss H (1990) Theor Chim Acta 77:123

    CAS  Google Scholar 

  28. Vahtras O, Almlöf J, Feyereisen MW (1993) Chem Phys Lett 213:514

    CAS  Google Scholar 

  29. Cossi M, Rega N, Scalmani G, Barone V (2003) J Comput Chem 24:669

    CAS  PubMed  Google Scholar 

  30. Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR (2012) J Cheminform 4:17

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Patel MN, Patel CR, Joshi HN, Thakor KP (2014) Spectrochim Acta, Part A 127:261

    CAS  Google Scholar 

  32. Lakowicz JR (1999) Principles of fluorescence spectroscopy, 2nd edn. Plenum Press, New York

    Google Scholar 

  33. Mosmann T (1983) J Immunol Methods 65:55

    CAS  Google Scholar 

  34. Deacon GB, Phillips R (1980) J Coord Chem Rev 33:227

    CAS  Google Scholar 

  35. Turel I (2002) Coord Chem Rev 232(1–2):27

    CAS  Google Scholar 

  36. Ya-Wen T, Yun-Fan C, Yong-Jie L, Kuan-Hung C, Lin C-H, Jui-Hsien H (2018) Molecules 23:159

    Google Scholar 

  37. Adebayo AA, Ajibade PA (2016) J Chem 2016:15, Article ID 3672062

  38. Son G, Yeo J, Kim M, Kim S, Holmen A, Akerman B, Norden B (1998) J Am Chem Soc 120:6451

    CAS  Google Scholar 

  39. Pyle AM, Rehmann JP, Meshoyrer R, Kumar CV, Turro NJ, Barton JK (1989) J Am Chem Soc 111:3051

    CAS  Google Scholar 

  40. Zhao G, Lin H, Zhu S, Sun H, Chen Y (1998) J Inorg Biochem 70:219

    CAS  PubMed  Google Scholar 

  41. Dhar S, Nethaji M, Chakravarty AR (2005) J Inorg Biochem 99:805

    CAS  PubMed  Google Scholar 

  42. Pasternack RF, Cacca M, Keogh B, Stephenson TA, Williams AP, Gibbs FJ (1991) J Am Chem Soc 113:6835

    CAS  Google Scholar 

  43. Lakowicz JR, Weber G (1973) Biochemistry 12:4161

    CAS  PubMed  Google Scholar 

  44. Satyanarayana S, Dabrowiak JC, Chaires JB (1993) Biochemistry 32:2573

    CAS  PubMed  Google Scholar 

  45. Kelly JM, Tossi AB, McConnell DJ (1985) Nucleic Acids Res 13:6017

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Suh D, Chaires JB (1995) Bioorg Med Chem 3:723

    CAS  PubMed  Google Scholar 

  47. Wang Y, Zhang H, Zhang G, Tao W, Tang S (2007) J Luminescence 126:211

    CAS  Google Scholar 

  48. Ahmad B, Parveen S, Khan RH (2006) Biomacromolecules 7:1350

    CAS  PubMed  Google Scholar 

  49. Mishra B, Barik A, Priyadarsini KI, Mohan H (2005) J Chem Sci 117:641

    CAS  Google Scholar 

  50. Petra H, Bock K, Atil B, Hoda MA, Korner W, Bartel C, Jungwirth U, Keppler BK, Michael M, Berger W, Gunda K (2010) J Biol Inorg Chem 15:737

    Google Scholar 

  51. Tan C, Hu S, Liu J, Liangnian J (2011) Eur J Med Chem 46:1555

    CAS  PubMed  Google Scholar 

  52. Wee HA, Elisa D, Claudine S, Rosario S, Lucienne J, Dyson PJ (2006) Inorg Chem 45:9006

    Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the University Grants Commission RFSMS-BSR fellowship [UGC No. F.4-1/2006 (BSR)/5-68/2007 (BSR)], New Delhi, for financial assistance. The authors are thankful to the Head, Department of Chemistry and Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, for providing us with the necessary laboratory facilities and required instrumentation facilities to carry out the research work. The authors thank DBT-MSUB-ILSPARE project, Dr. Vikram Sarabhai Science Block, M. S. University of Baroda, for providing the ESI MS analysis of the complexes and FACS analysis.

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Authors and Affiliations

  1. Department of Chemistry, The Maharaja Sayajirao University of Baroda, Vadodara, India

    Ramadevi Pulipaka, Soumya R. Dash, Priyanka Khanvilkar & Debjani Chakraborty

  2. Department of Zoology, The Maharaja Sayajirao University of Baroda, Vadodara, India

    Sarmita S. Jana & Ranjitsinh V. Devkar

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  1. Ramadevi Pulipaka
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Correspondence to Debjani Chakraborty.

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Pulipaka, R., Dash, S.R., Khanvilkar, P. et al. Design, synthesis and in vitro bioactivity of mixed ligand Ru(II) complexes bearing the fluoroquinolone antibacterial agents. Transit Met Chem 44, 721–735 (2019). https://doi.org/10.1007/s11243-019-00341-3

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