Screening organometallic thiophene containing thiosemicarbazone ruthenium (II/III) complexes as potential anti-tumour agents

  • Zehra Tavsan
  • Pelin Köse Yaman
  • Elif Subasi
  • Hulya Ayar Kayali
Original Paper
  • 104 Downloads

Abstract

The new ruthenium (III) complex has been synthesized and characterized by elemental analysis, FT-IR, UV–Vis, EI-Mass, EPR spectroscopy, and magnetic susceptibility measurement. Cytotoxic effects of organoruthenium (II/III) complexes 1a, 1b, and 2a, and their ligands (TSC1 and TSC2) in cultured human ovarian (A2780, SKOV-3, and OVCAR-3) and colon (DLD, CCD18Co, and Caco-2) cells have been investigated comparing reactivity of the Ru (II/III) complexes and their free TSC ligands. The complexes exhibit higher cytotoxicity in three cancer cell lines than in normal cells. The binding with CT-DNA and BSA of the all complexes were weak compared with their ligand in spite of the cellular uptake of these complexes into the cytoplasm and then nucleus while their cytotoxic effects were vice versa. All the results showed that Complex 1b has more efficient cytotoxicity on the colon cancer cells than ovarian cancer cells. However, Complex 2a is a better drug candidate especially for antitumor therapy of metastasized ovarian cancer.

Keywords

Ruthenium (II/III) thiosemicarbazone Synthesis Cytotoxicity Antitumor Colon cancer 

Notes

Acknowledgements

This study was supported by project number 215Z663 TUBITAK (The Scientific and Technological Research Council of Turkey), sincerely. We gratefully thank the Graduate School of Natural and Applied Sciences, Dokuz Eylül University, İzmir Biomedicine and Genome Center, Dokuz Eylül University and EBILTEM, Ege University. We also thank to Technician Birgül Kehlibar who made MTT analysis.

Supplementary material

775_2018_1549_MOESM1_ESM.pdf (346 kb)
Supplementary material 1 (PDF 345 kb)

References

  1. 1.
    Klayman DL, Scovill JP, Bartosevich JF, Bruce J (1983) J Med Chem 26:35–39CrossRefPubMedGoogle Scholar
  2. 2.
    Beraldo H, Gambino D (2004) MiniRev Med Chem 4:31–39CrossRefGoogle Scholar
  3. 3.
    Garcia-Tojal J, Garcia-Orad A, Serra JL, Pizarro JL, Lezamma L, Arriortua MI, Rojo T (1999) J Inorg Biochem 75:45–54CrossRefPubMedGoogle Scholar
  4. 4.
    Dobek AS, Klayman DL, Dickson ET, Scovill JP, Tramont EC (1980) Antimicrob Agents Chemother 18:27–36CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ramachandran R, Rani M, Kabilan S (2009) Bioorg Med Chem Lett 19:2819–2823CrossRefPubMedGoogle Scholar
  6. 6.
    Kovala-Demertzi D, Miller JR, Kourkoumelis N, Hadjikakou SK, Demertzis MA (1999) Polyhedron 18:1005–1013CrossRefGoogle Scholar
  7. 7.
    Finch RA, Liu MC, Grill SP, Rose WC, Loomis R, Vasquez KM, Cheng YC, Sartorelli AC (2000) Biochem Pharmacol 59:983–991CrossRefPubMedGoogle Scholar
  8. 8.
    Sharma S, Athar F, Maurya MR, Azam A (2005) Eur J Med Chem 40:1414–1419CrossRefPubMedGoogle Scholar
  9. 9.
    Parrilha GL, Da Silva JG, Gouveia LF, Gasparoto AK, Dias RP, Rocha WR, Santos DA, Speziali NL, Beraldo H (2011) Eur J Med Chem 46:1473–1482CrossRefPubMedGoogle Scholar
  10. 10.
    Alomar K, Gaumet V, Allain M, Bouet G, Landreau A (2012) J Inorg Biochem 115:36–43CrossRefPubMedGoogle Scholar
  11. 11.
    Shipman C Jr, Smith SH, Drach JC, Klayman DL (1986) Antivir Res 6:197–222CrossRefPubMedGoogle Scholar
  12. 12.
    Usman A, Razak IA, Chantrapromma S, Fun H-K, Sreekanth A, Sivakumar S, Kurup MRP (2002) Acta Crystallogr C 58:M461–M463CrossRefPubMedGoogle Scholar
  13. 13.
    Du J, Zhang E, Zhao Y, Zheng W, Zhang Y, Lin Y, Wang Z, Luo Q, Wu K, Wang F (2015) Metallomics 7:1573–1583CrossRefPubMedGoogle Scholar
  14. 14.
    Markowska A, Kasprzak B, Jaszczynska-Nowinka K, Lubin J, Markowska J (2015) Contemp Oncol 19:271–275Google Scholar
  15. 15.
    Meng X, Leyva ML, Jenny M, Gross I, Benosman S, Fricker B, Harlepp S, Hebraud P, Boos A, Wlosik P, Bischoff P, Sirlin C, Pfeffer M, Loeffler JP, Gaiddon C (2009) Cancer Res 69:5458–5466CrossRefPubMedGoogle Scholar
  16. 16.
    Muhammad N, Guo Z (2014) Curr Opin Chem Biol 19:144–153CrossRefPubMedGoogle Scholar
  17. 17.
    Oehninger L, Stefanopoulou M, Alborzinia H, Schur J, Ludewig S, Namikawa K, Munoz-Castro A, Koster RW, Baumann K, Wolfl S, Sheldrick WS, Ott I (2013) Dalton Trans 42:1657–1666CrossRefPubMedGoogle Scholar
  18. 18.
    Patil SA, Patil SA, Patil R, Keri RS, Budagumpi S, Balakrishna GR, Tacke M (2015) Future Med Chem 7:1305–1333CrossRefPubMedGoogle Scholar
  19. 19.
    Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7:573–584CrossRefPubMedGoogle Scholar
  20. 20.
    Bruijnincx PC, Sadler PJ (2008) Curr Opin Chem Biol 12:197–206CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kannarkat G, Lasher EE, Schiff D (2007) Curr Opin Neurol 20:719–725PubMedGoogle Scholar
  22. 22.
    Saygideger B, Keles T, Serindag O (2014) Bioinorg Chem Appl 2014:717421Google Scholar
  23. 23.
    Brescacin L, Masi A, Sava G, Bergamo A (2015) J Biol Inorg Chem 20:1163–1173CrossRefPubMedGoogle Scholar
  24. 24.
    Depenbrock H, Schmelcher S, Peter R, Keppler BK, Weirich G, Block T, Rastetter J, Hanauske AR (1997) Eur J Cancer 33:2404–2410CrossRefPubMedGoogle Scholar
  25. 25.
    Pampaloni G (2010) Coord Chem Rev 254:402–419CrossRefGoogle Scholar
  26. 26.
    Therrien B (2009) Coord Chem Rev 253:493–519CrossRefGoogle Scholar
  27. 27.
    Allardyce CS, Dorcier A, Scolaro C, Dyson PJ (2005) Appl Organomet Chem 19(1):1–10CrossRefGoogle Scholar
  28. 28.
    Yildirim H, Guler E, Yavuz M, Ozturk N, Yaman PK, Subasi E, Şahin E, Timur S (2014) Mater Sci Eng C 44:1–8CrossRefGoogle Scholar
  29. 29.
    Öztürk N, Yaman PK, Yavuz M, Öter Ö, Timur S, Subaşi E (2014) J Coord Chem 67(16):2688–2700CrossRefGoogle Scholar
  30. 30.
    Bennett MA, Huang TN, Matheson TW, Smith AK (1985) Inorg Synth 21:75–78Google Scholar
  31. 31.
    Jensen SB, Rodger SJ, Spicer MD (1998) J Organomet Chem 556(1):151–158CrossRefGoogle Scholar
  32. 32.
    Mandal SK, Chakravarty AR (1992) Polyhedron 11:823–827CrossRefGoogle Scholar
  33. 33.
    Yaman PK, Şen B, Karagöz CS, Subaşı E (2017) J Organomet Chem 832:27–35CrossRefGoogle Scholar
  34. 34.
    Klayman DL, Lin AJ, Acton N, Scovill JP, Hoch JM, Milhous WK (1984) J Nat Prod 47:715–717CrossRefPubMedGoogle Scholar
  35. 35.
    Scovill JP (1991) Phosphorus Sulfur Silicon Relat Elem. 60:15–19CrossRefGoogle Scholar
  36. 36.
    Perrin DD, Armarego WLF, Perrin DR (1980) Purification of laboratory chemicals, 2nd edn. Pergamon, OxfordGoogle Scholar
  37. 37.
    Sampath K, Sathiyaraj S, Raja G, Jayabalakrishnan C (2013) J Mol Struct 1046:82–91CrossRefGoogle Scholar
  38. 38.
    Winkhaus G, Singer H (1967) J Organomet Chem 7:487–491CrossRefGoogle Scholar
  39. 39.
    Manimaran A, Jayabalakrishnan C (2012) J Adv Res 3:233–236CrossRefGoogle Scholar
  40. 40.
    Natarajan K, Poddar RK, Agarwala U (1977) J Inorg Nucl Chem 39:431–435CrossRefGoogle Scholar
  41. 41.
    Auzias M, Therrien B, Süss-Fink G, Štěpnika P, Ang WH, Dyson PJ (2008) Inorg Chem 47:578–583CrossRefPubMedGoogle Scholar
  42. 42.
    Jayabalakrishnan C, Karvembu R, Natarajan K (2002) Transition Met Chem 27(7):790–794CrossRefGoogle Scholar
  43. 43.
    Singh S, Athar F, Maurya MR, Azam A (2006) Eur J Med Chem 41(5):592–598CrossRefPubMedGoogle Scholar
  44. 44.
    Karvembu R, Natarajan K (2002) Polyhedron 21(17):1721–1727CrossRefGoogle Scholar
  45. 45.
    Manivannan S, Prabhakaran R, Balasubramanian KP, Dhanabal V, Karvembu R, Chinnusamy V, Natarajan K (2007) Appl Organometal Chem 21:952–957CrossRefGoogle Scholar
  46. 46.
    Khan MMT, Srinivas D, Kureshy RI, Khan NH (1990) Inorg Chem 29:2320–2326CrossRefGoogle Scholar
  47. 47.
    Thangadurai TD, Natarajan K (2001) Transition Met Chem 26:717–722CrossRefGoogle Scholar
  48. 48.
    Ballhausen CJ (1962) Ligand field theory. MacGraw-Hill, New YorkGoogle Scholar
  49. 49.
    Ramesh R, Maheswaran S (2003) J Inorg Biochem 96:457–462CrossRefPubMedGoogle Scholar
  50. 50.
    Lever ABP (1984) Inorganic electronic spectroscopy, 2nd edn. Elsevier, New YorkGoogle Scholar
  51. 51.
    Pal S (2003) Eur J Inorg Chem 2003(23):4244–4252CrossRefGoogle Scholar
  52. 52.
    Mosmann T (1983) J Immunol Methods 65:55CrossRefPubMedGoogle Scholar
  53. 53.
    Esteghamat-Panah R, Hadadzadeh H, Farrokhpour H, Mortazavi M, Amirghofran Z (2017) Inorg Chim Acta 454:184–196CrossRefGoogle Scholar
  54. 54.
    Dong ZQ, Liu FM, Zeng YM (2011) J Chem Crystallogr 41(8):1158–1164CrossRefGoogle Scholar
  55. 55.
    Gonzaga D, da Silva FC, Ferreira VF, Wardell JL, Wardell SM (2016) J Chem Crystallogr 46(2):67–76CrossRefGoogle Scholar
  56. 56.
    Zhang QL, Liu JG, Chao H, Xue GQ, Ji LN (2001) J Inorg Biochem 83:49–55CrossRefPubMedGoogle Scholar
  57. 57.
    Gupta RK, Pandey R, Sharma G, Prasad R, Koch B, Srikrishna S, Li PZ, Xu Q, Pandey DS (2013) Inorg Chem 52:13984–13996CrossRefPubMedGoogle Scholar
  58. 58.
    Mancin F, Scrimin P, Tecilla P, Tonellato U (2005) Chem Commun 20:2540–2548CrossRefGoogle Scholar
  59. 59.
    Tjioe L, Meininger A, Joshi T, Spiccia L, Graham B (2011) Inorg Chem 50:4327–4339CrossRefPubMedGoogle Scholar
  60. 60.
    Shanmugapriya A, Kalaiarasi G, Kalaivani P, Dallemer F, Prabhakaran R (2016) Inorg Chim Acta 449:107–118CrossRefGoogle Scholar
  61. 61.
    Xiao L, Wang H, Zhang Q, Zhu Y, Luo J, Liang Y, Zhang S, Zhou H, Tian Y, Wu J (2015) Dyes Pigm 113:165–173CrossRefGoogle Scholar
  62. 62.
    Wolfe A, Shimer G Jr, Meehan T (1987) Biochemistry 26:6392–6396CrossRefPubMedGoogle Scholar
  63. 63.
    Gup R, Erer O, Dilek N (2017) J Mol Struct 1129:142–151CrossRefGoogle Scholar
  64. 64.
    Leung SK, Kwok KY, Zhang KY, Wing Lo KK (2010) Inorg Chem 49:4984–4995CrossRefPubMedGoogle Scholar
  65. 65.
    Muralisankar M, Sujith S, Bhuvanesh NSP, Sreekanth A (2016) Polyhedron 118:103–117CrossRefGoogle Scholar
  66. 66.
    Stern O, Volmer M (1919) Z Phys 20:183–188Google Scholar
  67. 67.
    Kathiravan A, Chandramohan M, Renganathan R, Sekar S (2009) J Mol Struct 919:210–214CrossRefGoogle Scholar
  68. 68.
    Lakowicz JR (1991) Principles of fluorescence spectroscopy. Springer, New YorkGoogle Scholar
  69. 69.
    Böhme U, Scheler U (2007) Chem Phys Lett 435:342–345CrossRefGoogle Scholar
  70. 70.
    Frasca D, Ciampa J, Emerson J, Umans RS, Clarke MJ (1996) Met Based Drugs 3:197–209CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Clarke MJ (2002) Coord Chem Rev 232:69–93CrossRefGoogle Scholar
  72. 72.
    Messori L, Vilchez FG, Vilaplana R, Piccioli F, Alessio E, Keppler B (2000) Met Based Drugs 7:335–342CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Messori L, Orioli P, Vullo D, Alessio E, Iengo E (2000) Eur J Biochem 267:1206–1213CrossRefPubMedGoogle Scholar
  74. 74.
    Groessl M, Reisner E, Hartinger CG, Eichinger R, Semenova O, Timerbaev AR, Jakupec MA, Arion VB, Keppler BK (2007) J Med Chem 50:2185–2193CrossRefPubMedGoogle Scholar
  75. 75.
    Yan YY, Su XD, Liang YJ, Zhang JY, Shi CJ, Lu Y, Gu LQ, Fu LW (2008) Mol Cancer Ther 7:1688–1697CrossRefPubMedGoogle Scholar

Copyright information

© SBIC 2018

Authors and Affiliations

  • Zehra Tavsan
    • 1
    • 3
  • Pelin Köse Yaman
    • 2
  • Elif Subasi
    • 2
  • Hulya Ayar Kayali
    • 2
    • 3
  1. 1.The Graduate School of Natural and Applied SciencesDokuz Eylül UniversityIzmirTurkey
  2. 2.Department of Chemistry, Faculty of ScienceDokuz Eylül UniversityIzmirTurkey
  3. 3.Izmir Biomedicine and Genome CenterIzmirTurkey

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