Skip to main content
SpringerLink
Log in

Synthesis and evaluation of new salicylaldehyde-2-picolinylhydrazone Schiff base compounds of Ru(II), Rh(III) and Ir(III) as in vitro antitumor, antibacterial and fluorescence imaging agents

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Reaction of salicylaldehyde-2-picolinylhydrazone (HL) Schiff base ligand with precursor compounds [{(p-cymene)RuCl2}2] 1, [{(C6H6)RuCl2}2] 2, [{Cp*RhCl2}2] 3 and [{Cp*IrCl2}2] 4 yielded the corresponding neutral mononuclear compounds 5–8, respectively. The in vitro antitumor evaluation of the compounds 1–8 against Dalton’s ascites lymphoma (DL) cells by fluorescence-based apoptosis study and by their half-maximal inhibitory concentration (IC50) values revealed the high antitumor activity of compounds 3, 4, 5 and 6. Compounds 1–8 render comparatively lower apoptotic effect than that of cisplatin on model non-tumor cells, i.e., peripheral blood mononuclear cells (PBMC). The antibacterial evaluation of compounds 5–8 by agar well-diffusion method revealed that compound 6 is significantly effective against all the eight bacterial species considered with zone of inhibition up to 35 mm. Fluorescence imaging study of compounds 5–8 with plasmid circular DNA (pcDNA) and HeLa RNA demonstrated their fluorescence imaging property upon binding with nucleic acids. The docking study with some key enzymes associated with the propagation of cancer such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II revealed strong interactions between proteins and compounds 5–8. Conformational analysis by density functional theory (DFT) study has corroborated our experimental observation of the N, N binding mode of ligand. Compounds 5–8 exhibited a HOMO (highest occupied molecular orbital)–LUMO (lowest unoccupied molecular orbital) energy gap 2.99–3.04 eV.

Graphical Abstract

Half-sandwich ruthenium, rhodium and iridium compounds were obtained by treatment of metal precursors with salicylaldehyde-2-picolinylhydrazone (HL) by in situ metal-mediated deprotonation of the ligand. Compounds under investigation have shown potential antitumor, antibacterial and fluorescence imaging properties. Arene ruthenium compounds exhibited higher activity compared to that of Cp*Rh/Cp*Ir in inhibiting the cancer cells growth and pathogenic bacteria. At a concentration 100 µg/mL, the apoptosis activity of arene ruthenium compounds, 5 and 6 (~30 %) is double to that of Cp*Rh/Cp*Ir compounds, 7 and 8 (~12 %). Among the four new compounds 5–8, the benzene ruthenium compound, i.e., compound 6 is significantly effective against the pathogenic bacteria under investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Abbreviations

AO:

Acridine orange

DFT:

Density functional theory

DL:

Dalton’s ascites lymphoma

DMSO:

Dimethyl sulfoxide

EtBr:

Ethidium bromide

FBS:

Fetal serum albumin

HOMO:

Highest occupied molecular orbital

LUMO:

Lowest unoccupied molecular orbital

PBS:

Phosphate-buffered saline

pcDNA:

Plasmid circular DNA

RPMI:

Roswell park memorial institute medium

TAE:

Tris-acetate EDTA

TDDFT:

Time-dependant density functional theory

References

  1. Jamieson ER, Lippard SJ (1999) Chem Rev 99:2467–2498

    Article  CAS  PubMed  Google Scholar 

  2. Siddik ZH (2003) Oncogene 22:7265–7279

    Article  CAS  PubMed  Google Scholar 

  3. Thompson CB (1995) Science 267:1456–1462

    Article  CAS  PubMed  Google Scholar 

  4. Dorr RT, Pinedo HM, Schornagel JH (1996) Platinum and other metal coordination compounds in cancer chemotherapy. Plenum, New York, p 131

    Book  Google Scholar 

  5. Clarke MJ (1980) Met Ions Biol Syst 1:231–283

    Google Scholar 

  6. Lin GJ, Jiang GB, Xie YY, Huang HL, Liang ZH, Liu YJ (2013) J Biol Inorg Chem 18:873–882

    Article  CAS  PubMed  Google Scholar 

  7. Han BJ, Jiang GB, Wang J, Li W, Huang HL, Liu YJ (2014) RSC Adv 4:40899–40906

    Article  CAS  Google Scholar 

  8. Jiang GB, Yao JH, Wang J, Li W, Han BJ, Lin GJ, Xie YY, Huang HL, Liu YJ (2014) New J Chem 38:2554–2563

    Article  CAS  Google Scholar 

  9. Bergamo A, Sava G (2011) Dalton Trans 40:7817–7823

    Article  CAS  PubMed  Google Scholar 

  10. Timerbaev AR, Hartinger CG, Aleksenko SS, Keppler BK (2006) Chem Rev 106:2224–2248

    Article  CAS  PubMed  Google Scholar 

  11. Kandioller W, Balsano E, Meier SM, Jungwirth U, Göschl S, Roller A, Jakupec MA, Berger W, Keppler BK, Hartinger CG (2013) Chem Commun 49:3348–3350

    Article  CAS  Google Scholar 

  12. Liu Z, Salassa L, Habtemariam A, Pizarro AM, Clarkson GJ, Sadler PJ (2011) Inorg Chem 50:5777–5783

    Article  CAS  PubMed  Google Scholar 

  13. Lucas SJ, Lord RM, Wilson RL, Phillips RM, Sridharan V, McGowan PC (2012) Dalton Trans 41:13800–13802

    Article  CAS  PubMed  Google Scholar 

  14. Prescott LM, Harley JP, Klein DA (1990) Microbiology, 2nd edn. WMC, Brown publishers, Oxford, p 328

    Google Scholar 

  15. Goldie H, Felix MD (1951) Cancer Res 11:73–80

    CAS  PubMed  Google Scholar 

  16. Gajendra G, Sharma G, Biplob K, Sunhong P, Lee SS, Kim JW (2013) New J Chem 37:2573–2581

    Article  Google Scholar 

  17. Jagessar RC, Gomathinayagam S (2012) JPCS 4:1–6

    Google Scholar 

  18. Lo KKW, Choi AW, Law WH (2012) Dalton Trans 41:6021–6047

    Article  CAS  PubMed  Google Scholar 

  19. Lo KKW, Lee TKM, Zhang KY (2006) Inorg Chim Acta 359:1845–1854

    Article  CAS  Google Scholar 

  20. Leung SK, Wok KY, Zhang KY, Lo KKW (2010) Inorg Chem 49:4984–4995

    Article  CAS  PubMed  Google Scholar 

  21. Ulbricht C, Beyer B, Friebe C, Winter A, Schubert US (2009) Adv Mater 21:4418–4441

    Article  CAS  Google Scholar 

  22. Lo KKW, Chung CK, Zhu N (2006) Chem Eur J 12:1500–1512

    Article  CAS  PubMed  Google Scholar 

  23. Lo KKW, Zhang KY, Chung CK, Wok KY (2007) Chem Eur J 13:7110–7120

    Article  CAS  PubMed  Google Scholar 

  24. Zhang KY, Li SPY, Zhu N, Or IWS, Cheung MSH (2010) Inorg Chem 49:2530–2540

    Article  CAS  PubMed  Google Scholar 

  25. Wu H, Yang T, Zhao Q, Zhou J, Li C (2011) Dalton Trans 40:1969–1976

    Article  CAS  PubMed  Google Scholar 

  26. Tan W, Zhou J, Li F, Yi T, Tian H (2011) Chem Asian J 6:1263–1268

    Article  CAS  PubMed  Google Scholar 

  27. Vueba ML, Pina ME, Batista LAE, Carvalho DJ (2008) Pharm Sci 97:845–849

    Article  CAS  Google Scholar 

  28. Grove H, Kelly TL, Thompson K, Zhao L, Xu Z, Abedin TSM, Miller DO, Goeta AE, Wilson C, Howard JAK (2004) Inorg Chem 43:4278–4288

    Article  CAS  PubMed  Google Scholar 

  29. Salassa L, Garino C, Albertino A, Volpi G, Nervi C, Gobetto R, Hardcastle KI (2008) Organometallics 27:1427–1435

    Article  CAS  Google Scholar 

  30. Garino C, Ruiu T, Salassa L, Albertino A, Volpi G, Nervi C, Gobetto R, Hardcastle KI (2008) Eur J Inorg Chem 36:3587–3591

    Article  Google Scholar 

  31. Garino C, Gobetto R, Nervi C, Salassa V, Rosenberg E, Ross JBA, Chu X, Hardcastle KI, Sabatini C (2007) Inorg Chem 46:8752–8762

    Article  CAS  PubMed  Google Scholar 

  32. Albertino A, Garino C, Ghiani S, Gobetto R, Nervi C, Salassa L, Rosenberg E, Sharmin A, Viscardi G, Buscaino R, Croce G, Milanesio M (2007) J Organomet Chem 692:1377–1391

    Article  CAS  Google Scholar 

  33. Angelis FD, Car R, Spiro TG (2003) J Am Chem Soc 125:15710–15711

    Article  PubMed  Google Scholar 

  34. Salassa L, Garino C, Salassa G, Gobetto R, Nervi C (2008) J Am Chem Soc 130:9590–9597

    Article  CAS  PubMed  Google Scholar 

  35. Salassa L, Garino C, Salassa G, Nervi C, Gobetto R, Lamberti C, Gianolio D, Bizzarri R, Sadler PJ (2009) Inorg Chem 48:1469–1481

    Article  CAS  PubMed  Google Scholar 

  36. Funaki T, Funakoshi H, Kitao O, Komatsuzaki NO, Kasuga K, Sayama K, Sugihara H (2012) Angew Chem Int Ed 51:7528–7531

    Article  CAS  Google Scholar 

  37. Perrin DD, Armarego WLF (1996) Purification of laboratory chemicals, 4th edn. Butterworths-Heinemann, London, p 416

    Google Scholar 

  38. Bennet MA, Huang TN, Matheson TW, Smith AK, Robertson GB (1982) Inorg Synth 21:74

    Google Scholar 

  39. White C, Yates A, Maitlis PM (1992) Inorg Synth 29:228

    Article  CAS  Google Scholar 

  40. Bai Y, Dang D, Cao X, Duan C, Meng Q (2006) Inorg Chem Commun 9:86–89

    Article  CAS  Google Scholar 

  41. (2004) Stoe & Cie, X–RED, version 1.28b, Program for data reduction and absorption correction. Stoe & Cie GmbH, Darmstadt, Germany

  42. Sheldrick GM (1997) SHELXL. University of Gottingen, Germany

    Google Scholar 

  43. Farrugia LJ (1997) J Appl Cryst 30:565–566

    Article  CAS  Google Scholar 

  44. Bruno IJ, Cole JC, Edgington PR, Macrae CF, Pearson J, McCabe P, Taylor R (2002) Acta Crystallogr B 58:389–397

    Article  PubMed  Google Scholar 

  45. Meech SR, Phillips DJ (1983) Photochem 23:193–217

    Article  CAS  Google Scholar 

  46. Mataga N, Kubota T (1970) In molecular interactions and electronic spectra. Marcel Dekker Inc., New York

    Google Scholar 

  47. Prasad SB, Verma AK (2013) Microsc Microanal 19:1–18

    Article  Google Scholar 

  48. Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, Shimada K, Sakamoto M, Hirohashi S, Ohashi Y, Kakizoe T (2000) Lancet 356:802–807

    Article  CAS  PubMed  Google Scholar 

  49. Perez C, Paul M, Bazerque P (1990) Acta Bio Med Exp 15:113–115

    Google Scholar 

  50. Becke AD (1993) J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  51. Becke AD (1988) Phys Rev A 38:3098–3100

    Article  CAS  PubMed  Google Scholar 

  52. Becke AD (1988) J Chem Phys 88:2547–2553

    Article  CAS  Google Scholar 

  53. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AZ, Bloino J, Zheng G (2010) GAUSSIAN 09 (Revision B. 01). Gaussian, Inc., Wallingford

    Google Scholar 

  54. Boyle NMO, Tenderholt AL, Langner KM (2008) J Comput Chem 29:839

    Article  Google Scholar 

  55. Thomsen R, Christensen MH (2006) J Med Chem 49:3315–3321

    Article  CAS  PubMed  Google Scholar 

  56. Verma AK, Prasad SB (2013) Anticancer Agents in Med Chem 13:1096–1114

    Article  CAS  Google Scholar 

  57. Singh KS, Caroll PJ, Rao KM (2005) Polyhedron 24:391–396

    Article  CAS  Google Scholar 

  58. Govindaswamy P, Canivet J, Suss-Fink G, Stepnicka P, Ludvik J, Rao KM (2007) J Organomet Chem 692:3664–3675

    Article  CAS  Google Scholar 

  59. Prasad K, Therrien B, Rao KM (2008) J Organomet Chem 693:3049–3059

    Article  CAS  Google Scholar 

  60. Prasad KT, Gupta G, Rao AV, Das B, Rao KM (2009) Polyhedron 28:2649–2654

    Article  CAS  Google Scholar 

  61. Habtemariam A, Melchart M, Fernández R, Rarsons S, Oswald V, Parkin A, Fabbiani FPA, Davidson JE, Dawson A, Aird RE, Jodrell DI, Sadler PJ (2006) J Med Chem 49:6858–6868

    Article  CAS  PubMed  Google Scholar 

  62. Liu J, Lu TB, Deng H, Ji LN, Qu LH, Zhou H (2003) Trans Metal Chem 28:116–121

    Article  CAS  Google Scholar 

  63. Singh P, Bhardwaj A (2008) Rev Med Chem 8:388–398

    Article  CAS  Google Scholar 

  64. Basu Baul TS, Paul A, Pellerito L, Scopelliti M, Singh P, Verma P, Duthie A, de Vos D, Tiekink ER (2011) Invest New Drugs 29:285–299

    Article  CAS  PubMed  Google Scholar 

  65. Nongbri SL, Das B, Rao KM (2012) J Chem Sci 124:1365–1375

    Article  CAS  Google Scholar 

Download references

Acknowledgments

K. M. Rao gratefully acknowledges financial support from the CSIR, New Delhi, through the Research Grants No. 01(2493)/11/EMR-II. P. N. Rao thanks UGC, New Delhi for providing fellowship in the form of JRF and SRF. We thank SAIF and DST-PURSE SCXRD of NEHU for collecting NMR and X-ray analysis data. We thank Dr. G. Narahari Sastry, IICT, Hyderabad, for providing facility to carry out DFT calculations, Mr. Veeranjaneylulu, IISc Bangalore for his support in various analyses, Dr. S. Mitra and Mr. Mullahmuhai for their help in fluorescence studies.

Author information

Authors and Affiliations

  1. Centre for Advanced Studies in Chemistry, North Eastern Hill University, Shillong, 793 022, India

    Narasinga Rao Palepu, S. L. Nongbri & Mohan Rao Kollipara

  2. Centre for Molecular Modeling, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India

    J. Richard Premkumar

  3. Department of Molecular Oncology, Cachar Cancer Hospital and Research Centre, Meherpur, Silchar, Cachar, 788015, Assam, India

    Akalesh Kumar Verma

  4. Department of Biotechnology and Bioinformatics, Microbiology Laboratory, North Eastern Hill University, Shillong, 793 022, India

    Kaushik Bhattacharjee & S. R. Joshi

  5. Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4M1, Canada

    Scott Forbes & Yurij Mozharivskyj

  6. Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, 793 022, India

    Romita Thounaojam & K. Aguan

Authors
  1. Narasinga Rao Palepu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. L. Nongbri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Richard Premkumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akalesh Kumar Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kaushik Bhattacharjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. R. Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Scott Forbes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yurij Mozharivskyj
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Romita Thounaojam
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K. Aguan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Mohan Rao Kollipara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohan Rao Kollipara.

Electronic supplementary material

Below is the link to the electronic supplementary material.

775_2015_1249_MOESM1_ESM.pdf

CCDC 1036511 [6], CCDC 1012445 [7] and 1012446 [8] contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif, by e-mailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033 (PDF 1001 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Palepu, N.R., Nongbri, S.L., Premkumar, J.R. et al. Synthesis and evaluation of new salicylaldehyde-2-picolinylhydrazone Schiff base compounds of Ru(II), Rh(III) and Ir(III) as in vitro antitumor, antibacterial and fluorescence imaging agents. J Biol Inorg Chem 20, 619–638 (2015). https://doi.org/10.1007/s00775-015-1249-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-015-1249-3

Keywords

Search

Navigation