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Tumor selective Ru(III) Schiff bases complexes with strong in vitro activity toward cisplatin-resistant MDA-MB-231 breast cancer cells

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Abstract

Novel ruthenium(III) complexes of general formula Na[RuCl2(L1−3-N,O)2] where L(1–3) denote deprotonated Schiff bases (HL1-HL3) derived from 5-substituted salicyladehyde and alkylamine (propyl- or butylamine) were prepared and characterized based on elemental analysis, mass spectra, infrared, electron spin/paramagnetic resonance (ESR/EPR) spectroscopy, and cyclovoltammetric study. Optimization of five isomers of complex C1 was done by DFT calculation. The interaction of C1–C3 complexes with DNA (Deoxyribonucleic acid) and BSA (Bovine serum albumin) was investigated by electron spectroscopy and fluorescence quenching. The cytotoxic activity of C1–C3 was investigated in a panel of four human cancer cell lines (K562, A549, EA.hy926, MDA-MB-231) and one human non-tumor cell line (MRC-5). Complexes displayed an apparent cytoselective profile, with IC50 values in the low micromolar range from 1.6 ± 0.3 to 23.0 ± 0.1 µM. Cisplatin-resistant triple-negative breast cancer cells MDA-MB-231 displayed the highest sensitivity to complexes, with Ru(III) compound containing two chlorides and two deprotonated N-propyl-5-chloro-salicylidenimine (hereinafter C1) as the most potent (IC50 = 1.6 µM), and approximately ten times more active than cisplatin (IC50 = 21.9 µM). MDA-MB-231 cells treated for 24 h with C1 presented with apoptotic morphology, as seen by acridine orange/ethidium bromide staining, while 48 h of treatment induced DNA fragmentation, and necrotic changes in cells, as seen by flow cytometry analysis. Drug-accumulation study by inductively coupled plasma mass spectrometry (ICP-MS) demonstrated markedly higher intracellular accumulation of C1 compared with cisplatin.

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The dataset generated and analyzed during the current study is available upon reasonable request.

References

  1. Clarke MJ (2003) Ruthenium metallopharmaceuticals. Coord Chem Rev 236(1–2):209–233

    Article  CAS  Google Scholar 

  2. Keppler B (1993) Metal complexes in cancer chemotherapy. VCH-Verlag, Weinheim, pp 1–42

    Google Scholar 

  3. Hartinger CG, Jakupec MA, Zorbas-Seifried S et al (2008) KP1019, a new redox-active anticancer agent—preclinical development and results of a clinical phase I study in tumor patients. Chem Biodivers 10:2140–2155. https://doi.org/10.1002/cbdv.200890195

    Article  Google Scholar 

  4. Alessio E, Mestroni G, Bergamo A et al (2004) Ruthenium antimetastatic agents. Curr Top Med Chem 4(15):1525–1535. https://doi.org/10.2174/1568026043387421

    Article  CAS  PubMed  Google Scholar 

  5. Clarke MJ, Bitler S, Rennert D et al (1980) Reduction and subsequent binding of ruthenium ions catalyzed by subcellular components. J Inotg Biochem 12(1):79–87. https://doi.org/10.1016/S0162-0134(00)80045-8

    Article  CAS  Google Scholar 

  6. Kahrović E, Zahirović A, Turkušić E et al (2016) A dinuclear ruthenium(II) Schiff base complex with dissimilar coordination: synthesis, characterization, and biological activity. Z Anorg Allg Chem 642(6):480–485. https://doi.org/10.1002/zaac.201600008

    Article  CAS  Google Scholar 

  7. Ljubijankić N, Zahirović A, Turkušić E et al (2013) DNA binding properties of two ruthenium(III) complexes containing Schiff bases derived from salicylaldehyde: spectroscopic and electrochemical evidence of CT DNA intercalation. Croat Chem Acta 86(2):215–222. https://doi.org/10.5562/cca2216

    Article  CAS  Google Scholar 

  8. Kahrović E, Zahirović A, Kraljević Pavelić S et al (2017) In vitro anticancer activity of binuclear Ru(II) complexes with Schiff bases derived from 5-substituted salicylaldehyde and 2-aminopyridine with notably low IC50 values. J Coord Chem 70(10):1683–1697. https://doi.org/10.1080/00958972.2017.1308503

    Article  CAS  Google Scholar 

  9. Muzika V, Custovic S, Alicelebic S et al (2019) Dinuclear ruthenium(II) Schiff base complex: a first in vivo study in Swiss albino mice. Bratisl Med J 120(01):26–34. https://doi.org/10.4149/BLL_2019_004

    Article  CAS  Google Scholar 

  10. Perdew JP (1991) Electronic Structure of Solids ‘91,. In: Ziesche P, Eschrig H (eds) 11, and subsequent references. Akademie Verlag, Berlin

  11. Adamo C, Barone V (1998) Exchange functionals with improved long-range behavior and adiabatic connection methods without adjustable parameters: the mPW and mPW1PW models. J Chem Phys 108:664–675. https://doi.org/10.1063/1.475428

    Article  CAS  Google Scholar 

  12. Hay PJ, Wadt WR (1985) Ab initio effective core potentials for molecular calculations—potentials for the transition-metal atoms Sc to Hg. J Chem Phys 82:270–283. https://doi.org/10.1063/1.448799

    Article  CAS  Google Scholar 

  13. Petersson GA, Al-Laham MA (1991) A complete basis set model chemistry. II. Open-shell systems and the total energies of the first-row atoms. J Chem Phys 94:6081–6090. https://doi.org/10.1063/1.460447

    Article  CAS  Google Scholar 

  14. Cossi M, Rega N, Scalmani G et al (2003) Energies, structures, and electronic properties of molecules in solution with the C-PCM solvation model. J Comput Chem 24:669–681. https://doi.org/10.1002/jcc.10189

    Article  CAS  PubMed  Google Scholar 

  15. Miertuš S, Scrocco E, Tomasi J (1981) Electrostatic interaction of a solute with a Continuum. A direct utilization of ab initio molecular potentials for the prevision of solvent effects. Chem Phys 55:117–129. https://doi.org/10.1016/0301-0104(81)85090-2. (And subsequent references)

    Article  Google Scholar 

  16. Frisch MJ et al. (2019) Gaussian 16, Revision C.01. Gaussian, Inc., Wallingford

  17. https://www.sdsc.edu/services/hpc/expanse/index.html. Accessed Dec 2022

  18. Rosenberg B, VanCamp L, Trosko JE et al (1969) Platinum compounds: a new class of potent antitumour agents. Nature 222:385–386. https://doi.org/10.1038/222385a0

    Article  CAS  PubMed  Google Scholar 

  19. Supino R (1995) Methods in molecular biology. In: O’Hare S, Atterwill S (eds) In vitro toxicity testing protocols, vol 43. C. K. Humana Press, Clifton, pp 137–149

    Chapter  Google Scholar 

  20. Ormerod MG (1994) Analysis of DNA-general methods. In: Ormerod MG (ed) In flow cytometry, a practical approach. Oxford University Press, New York, pp 119–125

    Google Scholar 

  21. Spector DL, Goldman RD, Leinwand LA (1998) Culture and biochemical analysis of cells. In: Cells: A Laboratory Manual, vol 1. Cold Spring Harbor Laboratory Press, New York

  22. Slee EA, Zhu H, Chow SC et al (1996) Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem J 315(1):21–24. https://doi.org/10.1042/bj3150021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dodo K, Katoh M, Shimizu T (2005) Inhibition of hydrogen peroxide-induced necrotic cell death with 3-amino-2-indolylmaleimide derivatives. Bioorg Med Chem Lett 15(12):3114–3118. https://doi.org/10.1016/j.bmcl.2005.04.016

    Article  CAS  PubMed  Google Scholar 

  24. Pavlović M, Nikolić S, Gligorijević N et al (2019) New organoruthenium compounds with pyrido[2′,3′:5,6]pyrazino[2,3-f][1, 10]phenanthroline: synthesis, characterization, cytotoxicity, and investigation of mechanism of action. J Biol Inorg Chem 24(2):297–310. https://doi.org/10.1007/s00775-019-01647-4

    Article  CAS  PubMed  Google Scholar 

  25. Eruslanov E, Kusmartsev S (2009) Identification of ROS using oxidized DCFDA and flow-cytometry. In: Armstrong D (ed) Advanced protocols in oxidative stress II, methods in molecular biology, vol 594. D. Humana Press, Totowa, pp 57–72. https://doi.org/10.1007/978-1-60761-411-1_4

    Chapter  Google Scholar 

  26. Kahrović E (2014) Ruthenium compounds with Schiff bases: design and promising application of salicylideneimine complexes. In: Keller GP (ed) Ruthenium synthesis, physicochemical properties and applications. NOVA Science Publishers, New York, pp 269–284

    Google Scholar 

  27. Vargiu AV, Robertazzi A, Magistrato A et al (2008) The hydrolysis mechanism of the anticancer ruthenium drugs NAMI-A and ICR investigated by DFT−PCM calculations. J Phys Chem B 112(14):4401–4409. https://doi.org/10.1021/jp710078y

    Article  CAS  PubMed  Google Scholar 

  28. Kannan S, Ramesh R (2006) Synthesis, characterization, catalytic oxidation and biological activity of ruthenium(III) Schiff base complexes derived from 3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione. Polyhedron 25(16):3095–3103. https://doi.org/10.1016/j.poly.2006.05.042

    Article  CAS  Google Scholar 

  29. Sivagamasundari M, Ramesh R (2007) Luminescent property and catalytic activity of Ru(II) carbonyl complexes containing N, O donor of 2-hydroxy-1-naphthylideneimines. Spectrochim Acta A Mol Biomol Spectrosc 67(1):256–262. https://doi.org/10.1016/j.saa.2006.03.017

    Article  CAS  PubMed  Google Scholar 

  30. Biswas N, Saha S, Zangrando E et al (2021) Catecholase-like activity and theoretical study in solid state of a new Ru(III)-Schiff base complex. Acta Chim Slov 68(1):212–221. https://doi.org/10.17344/acsi.2020.6379

    Article  CAS  PubMed  Google Scholar 

  31. Chen C, Ji J, Wang CJ (2020) Synthesis, characterization and crystal structures of half-sandwich ruthenium complexes with bidentate chiral Schiff-base ligands. J Organomet Chem 910:121129. https://doi.org/10.1016/j.jorganchem.2020.121129

    Article  CAS  Google Scholar 

  32. Wu F, Wang CJ, Lin H et al (2018) Syntheses, characterization and crystal structures of ruthenium(II)/(III) complexes with tridentate salicylaldiminato ligands. J Coord Chem 71(2):219–230. https://doi.org/10.1080/00958972.2017.1423476

    Article  CAS  Google Scholar 

  33. Zahirović A, Žilić D, Kraljević Pavelić S et al (2019) Type of complex-BSA binding forces affected by different coordination modes of alliin in novel water-soluble ruthenium complexes. New J Chem 43(15):5791–5804. https://doi.org/10.1039/C9NJ00826H

    Article  Google Scholar 

  34. Pushkar Y, Moonshiram D, Purohit V et al (2014) Spectroscopic analysis of catalytic water oxidation by [RuII(bpy)(tpy)H2O]2+ suggests that RuV=O is not a rate-limiting intermediate. J Am Chem Soc 136(34):11938–11945. https://doi.org/10.1021/ja506586b

    Article  CAS  PubMed  Google Scholar 

  35. Planas N, Vigara L, Cady C et al (2011) Electronic structure of oxidized complexes derived from cis-[RuII(bpy)2(H2O)2]2+and its photoisomerization mechanism. Inorg Chem 50(21):11134–11142. https://doi.org/10.1021/ic201686c

    Article  CAS  PubMed  Google Scholar 

  36. Daniel Q, Huang P, Fan T et al (2017) Rearranging from 6- to 7-coordination initiates the catalytic activity: an EPR study on a Ru-bda water oxidation catalyst. Coord Chem Rev 346:206–215. https://doi.org/10.1016/j.ccr.2017.02.019

    Article  CAS  Google Scholar 

  37. Stoll S, Schweige A (2006) EasySpin, a comprehensive software package for spectral simulation and analysis in EPR. J Magn Reson 178(1):42–55. https://doi.org/10.1016/j.jmr.2005.08.013

    Article  CAS  PubMed  Google Scholar 

  38. Szymańska B, Skrzypek D, Kovala-Demertzi D et al (2006) Synthesis and spectroscopic study of copper(II) and manganese(II) complexes with pipemidic acid. Spectrochim Acta A Mol Biomol Spectrosc 63(3):518–523. https://doi.org/10.1016/j.saa.2005.05.038

    Article  CAS  PubMed  Google Scholar 

  39. Munshi P, Samanta R, Kumar LG (1999) Paramagnetic ruthenium(III) ortho-metallated complexes. Synthesis, spectroscopic and redox properties. J Organomet 586(2):176–183. https://doi.org/10.1016/S0022-328X(99)00261-2

    Article  CAS  Google Scholar 

  40. Webb MI, Walsby CJ (2013) EPR as a probe of the intracellular speciation of ruthenium(III) anticancer compounds. Metallomics 5(12):1624–1633. https://doi.org/10.1039/C3MT00090G

    Article  CAS  PubMed  Google Scholar 

  41. Canevali C, Chiodini N, Morazzoni F et al (2000) Electron paramagnetic resonance characterization of ruthenium-dispersed tin oxide obtained by sol–gel and impregnation methods. J Mater Chem 10(3):773–778. https://doi.org/10.1039/A907947E

    Article  CAS  Google Scholar 

  42. Schluga P, Hartinger CG, Egger A et al (2006) Redox behavior of tumor-inhibiting ruthenium(III) complexes and effects of physiological reductants on their binding to GMP. Dalton Trans 6(14):1796–1802. https://doi.org/10.1039/b511792e

    Article  CAS  Google Scholar 

  43. Mandler D (2010) Anal bioanal chem. In: Scholz F (ed) Electroanalytical methods Guide to experiments and applications, vol 398(7-8), 2nd edn. Springer, Berlin, pp 2771–2772. https://doi.org/10.1007/s00216-010-4195-5

    Chapter  Google Scholar 

  44. Jabłońska-Wawrzycka A, Rogala P, Michałkiewicz S et al (2013) Ruthenium complexes in different oxidation states: synthesis, crystal structure, spectra and redox properties. Dalton Trans 42(17):6092–6101. https://doi.org/10.1039/C3DT32214A

    Article  PubMed  Google Scholar 

  45. Reisner E, Arion VB, Guedes da Silva MFC et al (2004) Tuning of redox potentials for the design of ruthenium anticancer drugs—an electrochemical study of [trans-RuCl4L(DMSO)]-and [trans-RuCl4L2]-complexes, where L = Imidazole, 1,2,4-Triazole, Indazole. Inorg Chem 43(22):7083–7093. https://doi.org/10.1021/ic049479c

    Article  CAS  PubMed  Google Scholar 

  46. Mestroni G, Alessio E, Sava G et al (1994) Water-soluble ruthenium(III)-dimethyl sulfoxide complexes: chemical behaviour and pharmaceutical properties. Met Based Drugs 1(1):41–63. https://doi.org/10.1155/MBD.1994.41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wiśniewska J, Fandzloch M, Muzioł T et al (2019) The hydrolysis of a ruthenium(III) complex with triazolopyrimidine ligands and mechanistic insights into its anticancer activity. Inorg Chem Commun 109:107567. https://doi.org/10.1016/j.inoche.2019.107567

    Article  CAS  Google Scholar 

  48. Azam M, Hussain Z, Warad I et al (2012) Novel Pd(II)–salen complexes showing high in vitro anti-proliferative effects against human hepatoma cancer by modulating specific regulatory genes. Dalton Trans 41(35):10854–10864. https://doi.org/10.1039/C2DT31143G

    Article  CAS  PubMed  Google Scholar 

  49. Long EC, Barton JK (1990) On demonstrating DNA intercalation. Acc Chem Res 23(9):271–273. https://doi.org/10.1021/ar00177a001

    Article  CAS  Google Scholar 

  50. Cory M, McKee DD, Kagan J et al (1985) Design, synthesis, and DNA binding properties of bifunctional intercalators. Comparison of polymethylene and diphenyl ether chains connecting phenanthridine. J Am Chem Soc 107(8):2528–2536. https://doi.org/10.1021/ja00294a054

    Article  CAS  Google Scholar 

  51. Brabec V, Kasparkova J (2018) Ruthenium coordination compounds of biological and biomedical significance. DNA binding agents. Coord Chem Rev 376:75–94. https://doi.org/10.1016/j.ccr.2018.07.012

    Article  CAS  Google Scholar 

  52. Patel MN, Parmar PA, Gandhi DS (2011) Synthesis, characterization and DNA binding and cleavage properties of ruthenium(II) complexes with various polypyridyls. J Enzyme Inhib Med Chem 26(5):734–741. https://doi.org/10.3109/14756366.2011.570007

    Article  CAS  PubMed  Google Scholar 

  53. Jiang CW, Chao H, Li H, Ji LN (2003) Syntheses, characterization and DNA-binding studies of ruthenium(II) terpyridine complexes: [Ru(tpy)(PHBI)]2+ and [Ru(tpy)(PHNI)]2+. J Inorg Biochem 93(3–4):247–255. https://doi.org/10.1016/s0162-0134(02)00577-9

    Article  CAS  PubMed  Google Scholar 

  54. Yin HJ, Zhang AG, Gao LH et al (2019) (2019) DNA groove-binding and acid-base properties of a Ru(II) complex containing anthryl moieties. Nucleosides Nucleotides Nucleic Acids. https://doi.org/10.1080/15257770.2019.1669804

    Article  PubMed  Google Scholar 

  55. Ramezanpour A, Karami K, Kharaziha M et al (2021) A mononuclear PdII complex with Naphcon; crystal structure, experimental and computational studies of the interaction with DNA/BSA and evaluation of anticancer activity. Polyhedron 206:115333. https://doi.org/10.1016/j.poly.2021.115333

    Article  CAS  Google Scholar 

  56. Li Y, Yang Z, Zhou M et al (2017) Synthesis and crystal structure of new monometallic Ni(ii) and Co(ii) complexes with an asymmetrical aroylhydrazone: effects of the complexes on DNA/protein binding property, molecular docking, and in vitro anticancer activity. RSC Adv 7(78):49404–49422. https://doi.org/10.1039/C7RA10283F

    Article  CAS  Google Scholar 

  57. Senthil RD, Bhuvanesh NSP, Natarajan K (2011) Effect of N(4)-phenyl substitution in 2-Oxo-1,2-dihydroquinoline-3-carbaldehyde semicarbazones on the structure, DNA/protein interaction, and antioxidative and cytotoxic activity of Cu(II) complexes. Inorg Chem 50(24):12852–12866. https://doi.org/10.1021/ic2020308

    Article  CAS  Google Scholar 

  58. Grigoryan KR, Aznauryan AG, Bagramyan NA et al (2008) Spectroscopic determination of binding between human serum albumin and a platinum(II) dimethylsulfoxide complex. J Appl Spectrosc 75(4):593–596. https://doi.org/10.1007/s10812-008-9070-1

    Article  CAS  Google Scholar 

  59. Grigoryan KR, Kazaryan AG (2009) Interaction of dimethylsulfoxide and diethylsulfoxide complexes of platinum(II) with bovine serum albumin. JAppl Spectrosc 76(4):607–610. https://doi.org/10.1007/s10812-009-9241-8

    Article  CAS  Google Scholar 

  60. Maikoo S, Chakraborty A, Vukea N et al (2021) Ruthenium complexes with mono- or bis-heterocyclic chelates: DNA/BSA binding, antioxidant and anticancer studies. J Biomol Struct Dyn 39:4077–4088. https://doi.org/10.1080/07391102.2020.1775126

    Article  CAS  PubMed  Google Scholar 

  61. Sauer M, Hofkens J, Enderlein J (2011) Basic principles of fluorescence spectroscopy. Wiley, New York. https://doi.org/10.1002/9783527633500.ch1

    Book  Google Scholar 

  62. Lakowicz JR (2006) Principles of fluorescence spectroscopy. Springer, Berlin

    Book  Google Scholar 

  63. Pauzi AZ, Yeap SK, Abu N et al (2016) Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro. Chin Med 15(11):46. https://doi.org/10.1186/s13020-016-0118-5

    Article  CAS  Google Scholar 

  64. Nikolic S, Opsenica D, Filipović V et al (2015) Strong in vitro cytotoxic potential of new ruthenium−cymene complexes. Organometallics 34:3464–3473. https://doi.org/10.1021/acs.organomet.5b00041

    Article  CAS  Google Scholar 

  65. Barr MP, Gray SG, Hoffmann AC et al (2013) Generation and characterisation of cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature. PLoS One 8(1):e54193. https://doi.org/10.1371/journal.pone.0054193

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Baharuddin P, Satar N, Fakiruddin KS et al (2016) Curcumin improves the efficacy of cisplatin by targeting cancer stem-like cells through p21 and cyclin D1-mediated tumour cell inhibition in non-small cell lung cancer cell lines. Oncol Rep 35:13–25. https://doi.org/10.3892/or.2015.4371

    Article  CAS  PubMed  Google Scholar 

  67. Ban KA, Godellas CV (2014) Epidemiology of breast cancer. Surg Oncol Clin N Am 23(3):409–422. https://doi.org/10.1016/j.soc.2014.03.011

    Article  PubMed  Google Scholar 

  68. Hongthong K, Ratanaphan A (2016) BRCA1-associated triple-negative breast cancer and potential treatment for ruthenium-based compounds. Curr Cancer Drug Target 16(7):606–617. https://doi.org/10.2174/1568009616666160203113957

    Article  CAS  Google Scholar 

  69. Pavlović M, Tadić A, Gligorijević N et al (2020) Synthesis, chemical characterization, PARP inhibition, DNA binding and cellular uptake of novel ruthenium(II)-arene complexes bearing benzamide derivatives in human breast cancer cells. J Inorg Biochem. https://doi.org/10.1016/j.jinorgbio.2020.111155

    Article  PubMed  Google Scholar 

  70. Tadić A, Poljarević J, Krstić M et al (2018) Ruthenium-arene complexes with NSAIDs: synthesis, characterization and bioactivity. New J Chem 42(4):3001–3019. https://doi.org/10.1039/c7nj04416j

    Article  CAS  Google Scholar 

  71. Galluzzi L, Senovilla L, Vitale I et al (2012) Molecular mechanisms of cisplatin resistance. Oncogene 31(15):1869–1883. https://doi.org/10.1038/onc.2011.384

    Article  CAS  PubMed  Google Scholar 

  72. Huang X, Halicka HD, Traganos F et al (2005) Cytometric assessment of DNA damage in relation to cell cycle phase and apoptosis. Cell Prolif 38(4):223–243. https://doi.org/10.1111/j.1365-2184.2005.00344.x

    Article  PubMed  PubMed Central  Google Scholar 

  73. Kumari S, Badana AK, Murali Mohan G et al (2018) Reactive oxygen species: a key constituent in cancer survival. Biomark Insights 13:1–9. https://doi.org/10.1177/1177271918755

    Article  Google Scholar 

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Acknowledgements

This work was supported by the Federal Ministry of Education and Science of Bosnia and Herzegovina (Grant no. 05-39-2619-1/18) and by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant no. III 41026 and Agreement no. 451-03-68/2022-14/200043). Computational resources in this study were procured through the NSF XSEDE grant (MCB140083) awarded to P.I. We thank Biljana Dojčinović for the ICP-MS measurements, Adnan Zahirović and Irnesa Osmanković for their support in measuring BSA and DNA interactions.

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Authors and Affiliations

  1. Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia

    Marijana Pavlović, Sandra Aranđelović & Siniša Radulović

  2. Laboratory for Inorganic and Bioinorganic Chemistry, Department of Chemistry, Faculty of Science, University of Sarajevo, Zmaja od Bosne 33, 71 000, Sarajevo, Bosnia and Herzegovina

    Emira Kahrović & Nevzeta Ljubijankić

  3. Faculty of Chemistry, University of Belgrade, Studentski Trg 12-16, Belgrade, Serbia

    Sanja Grgurić-Šipka

  4. Ruđer Bošković Institute, Bijenička 54, Zagreb, Croatia

    Dijana Žilić & Jurica Jurec

  5. Department of Natural Sciences, Weissman School of Arts and Sciences, Baruch College/CUNY, New York City, NY, USA

    Predrag-Peter Ilich

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Contributions

EK: design and development of compounds, interactions, supervision, writing—original draft, visualization, writing—review of chemical part. NL: syntheses. DŽ and JJ: X-band ESR spectroscopy, measurements and writing. P-PI: electronic structure calculations. MP: methodology, formal analysis and investigation, visualization, writing—original draft, writing—review and editing (biological part). SA: conceptualization, writing—review and editing (biological part). SR: conceptualization, funding acquisition, supervision. SG-Š: conceptualization, writing—review and editing.

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Pavlović, M., Kahrović, E., Aranđelović, S. et al. Tumor selective Ru(III) Schiff bases complexes with strong in vitro activity toward cisplatin-resistant MDA-MB-231 breast cancer cells. J Biol Inorg Chem 28, 263–284 (2023). https://doi.org/10.1007/s00775-023-01989-0

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