Skip to main content

Advertisement

SpringerLink
Log in

Synthesis, HSA-Binding and Anticancer Properties of [Cu2(\(\mu\)-dppm)2(N^N)2]2+

  • Published:
Journal of Inorganic and Organometallic Polymers and Materials Aims and scope Submit manuscript

Abstract

A set of dinuclear copper(I) complexes with the general formula [Cu2(μ-dppm)2(N^N)2]2+ were synthesized and characterized by 1HNMR, 31PNMR, and elemental analysis. The high-resolution mass spectra clearly illustrated isotopic pattern for the proposed dinuclear systems. The binding of the complexes toward human serum albumin (HSA) were evaluated, highlighting good binding affinities influenced by the nature of the substituted-diimine. The complexes induce changes in both the α-helix and the microenvironment structures of HSA. The HSA-bindings were modelled by molecular docking; [Cu2(μ-dppm)2(dppz)2][ClO4]2 (3) displays the highest binding score toward HSA due to the ability of dppz in establishing π-interactions. The anticancer properties of 1, 2 and 3 were screened against COLO 205, RCC-PR, HepGII and LLC-MK2 cell lines and the results were discussed. Complex 3 has better IC50 against all the cancer cell lines than that observed for cisplatin, but still lower than the cytotoxicity of Sunitinib. Moreover, complex 3 has higher selectivity towards cancer cells over normal cells when compared to cisplatin and sunitinib.

Graphical Abstract

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
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

HAS:

Human serum albumin

COLO-205:

Human colon carcinoma

RCC-PR:

Human kidney clear cell carcinoma

HepGII:

Liver hepatocellular carcinoma

LLC-MK2:

Rhesus monkey kidney epithelial normal cells

References

  1. B. Babgi, Synthetic protocols and applications of copper(I) phosphine and copper(I) phosphine/diimine complexes. J. Organomet. Chem. 956, 122124 (2021)

    Article  CAS  Google Scholar 

  2. G. Mani, V. Subramaniyan, Chapter 8 - Homoleptic and heteroleptic copper(I) complexes bearing diimine-diphosphine ligands, in Copper(I) Chemistry of Phosphines, Functionalized Phosphines and Phosphorus Heterocycles. ed. by M.S. Balakrishna (Elsevier, Amsterdam, 2019), pp. 237–258

    Chapter  Google Scholar 

  3. F. Tisato, M. Porchia, C. Santini, V. Gandin, C. Marzano, Chapter 3 - Phosphine–copper(I) complexes as anticancer agents: design, synthesis, and physicochemical characterization. Part I, in Copper(I) Chemistry of Phosphines, Functionalized Phosphines and Phosphorus Heterocycles. ed. by M.S. Balakrishna (Elsevier, Amsterdam, 2019), pp. 61–82

    Chapter  Google Scholar 

  4. C. Marzano, F. Tisato, M. Porchia, M. Pellei, V. Gandin, Chapter 4 - Phosphine copper(I) complexes as anticancer agents: biological characterization. Part II, in Copper(I) Chemistry of Phosphines, Functionalized Phosphines and Phosphorus Heterocycles. ed. by M.S. Balakrishna (Elsevier, Amsterdam, 2019), pp. 83–107

    Chapter  Google Scholar 

  5. L. Colina-Vegas, W. Villarreal, M. Navarro, Chapter 5 - Copper(I)–phosphine complexes: a promising approach in the search for antitumor agents, in Copper(I) Chemistry of Phosphines, Functionalized Phosphines and Phosphorus Heterocycles. ed. by M.S. Balakrishna (Elsevier, Amsterdam, 2019), pp. 109–143

    Chapter  Google Scholar 

  6. E. Wong, C.M. Giandomenico, Current status of platinum-based antitumor drugs. Chem. Rev. 99, 2451–2466 (1999)

    Article  CAS  PubMed  Google Scholar 

  7. A.S. Abu-Surrah, M. Kettunen, Platinum group antitumor chemistry: design and development of new anticancer drugs complementary to cisplatin. Curr. Med. Chem. 13, 1337–1357 (2006)

    Article  CAS  PubMed  Google Scholar 

  8. C.A. Rabik, M.E. Dolan, Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat. Rev. 33, 9–23 (2007)

    Article  CAS  PubMed  Google Scholar 

  9. R. Starosta, K. Stokowa, M. Florek, J. Król, A. Chwiłkowska, J. Kulbacka, J. Saczko, J. Skała, M. Jeżowska-Bojczuk, Biological activity and structure dependent properties of cuprous iodide complexes with phenanthrolines and water soluble tris (aminomethyl) phosphanes. J. Inorg. Biochem. 105, 1102–1108 (2011)

    Article  CAS  PubMed  Google Scholar 

  10. K.H. Mashat, B.A. Babgi, M.A. Hussien, M.N. Arshad, M.H. Abdellattif, Synthesis, structures, DNA-binding and anticancer activities of some copper (I)-phosphine complexes. Polyhedron 158, 164–172 (2019)

    Article  CAS  Google Scholar 

  11. B.A. Babgi, K.H. Mashat, M.H. Abdellattif, M.N. Arshad, K.A. Alzahrani, A.M. Asiri, J. Du, M.G. Humphrey, M.A. Hussien, Synthesis, structures, DNA-binding, cytotoxicity and molecular docking of CuBr (PPh3)(diimine). Polyhedron 192, 114847 (2020)

    Article  CAS  Google Scholar 

  12. S. Alsaedi, B.A. Babgi, M.H. Abdellattif, M.N. Arshad, A.-H.M. Emwas, M. Jaremko, M.G. Humphrey, A.M. Asiri, M.A. Hussien, DNA-binding and cytotoxicity of copper (I) complexes containing functionalized dipyridylphenazine ligands. Pharmaceutics 13, 764 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. J. Fernandez-Gallardo, B.T. Elie, M. Sanaú, M. Contel, Versatile synthesis of cationic N-heterocyclic carbenee gold(I) complexes containing a second ancillary ligand. Design of heterobimetallic rutheniumegold anticancer agents. Chem. Commun. 52, 3155–3158 (2016)

    Article  CAS  Google Scholar 

  14. L. Massai, J. Fernandez-Gallardo, A. Guerri, A. Arcangeli, S. Pillozzi, M. Contel, L. Messori, Design, synthesis and characterisation of new chimeric ruthenium(II)-gold(I) complexes as improved cytotoxic agents. Dalton Trans. 44, 11067–11076 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. M. Odachowski, C. Marschner, B. Blom, A review on 1, 1-bis (diphenylphosphino) methane bridged homo-and heterobimetallic complexes for anticancer applications: Synthesis, structure, and cytotoxicity. Eur. J. Med. Chem. 2020, 112613 (2020)

    Article  Google Scholar 

  16. M.S. Alsaeedi, B.A. Babgi, M.A. Hussien, M.H. Abdellattif, M.G. Humphrey, DNA-binding and anticancer activity of binuclear gold(I) alkynyl complexes with a phenanthrenyl bridging ligand. Molecules 25, 1033 (2020)

    Article  CAS  PubMed Central  Google Scholar 

  17. G.B. Jacobsen, B.L. Shaw, M. Thornton-Pett, Rhodium(I)-iron(0) carbonyl complexes containing one bridging Ph2PCH2PPh2 ligand, including the formation of a tetranuclear cluster from a heterobimetallic precursor: crystal structures of [(OC)4Fe(μ-Ph2PCH2PPh2)RhCl(CO)] and [Fe2Rh2(μ-Ph2PCH2PPh2)2(CO)8]. J. Chem. Soc. Dalton Trans. 11, 2751–2755 (1987)

    Article  Google Scholar 

  18. C. Lecomte, S. Skoulika, P. Aslanidis, P. Karagiannidis, S. Papastefanou, Copper(I) bromide complexes with heterocyclic thiones and triphenylphosphine as ligands. The X-ray crystal structure of copper(I) pyrimidine-2-thione bis (triphenylphosphine) bromide [Cu(PPh3)2(PymtH)Br]. Polyhedron 8, 1103–1109 (1989)

    Article  CAS  Google Scholar 

  19. I. Ascone, L. Messori, A. Casini, C. Gabbiani, A. Balerna, F. Dell’Unto, A.C. Castellano, Exploiting soft and hard X-ray absorption spectroscopy to characterize metallodrug/protein interactions: the binding of [trans-RuCl4(Im)(dimethylsulfoxide)][ImH] (Im = imidazole) to bovine serum albumin. Inorg. Chem. 47, 8629–8634 (2008)

    Article  CAS  PubMed  Google Scholar 

  20. M. Groessl, M. Terenghi, A. Casini, L. Elviri, R. Lobinski, P.J. Dyson, Reactivity of anticancer metallodrugs with serum proteins: new insights from size exclusion chromatography-ICP-MS and ESI-MS. J. Anal. At. Spectrom. 25, 305–313 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. A.Y. Shmykov, V.N. Filippov, L.S. Foteeva, B.K. Keppler, A.R. Timerbaev, Toward high-throughput monitoring of metallodrug–protein interaction using capillary electrophoresis in chemically modified capillaries. Anal. Biochem. 379, 216–218 (2008)

    Article  CAS  PubMed  Google Scholar 

  22. A.R. Timerbaev, C.G. Hartinger, S.S. Aleksenko, B.K. Keppler, Interactions of antitumor metallodrugs with serum proteins: advances in characterization using modern analytical methodology. Chem. Rev. 106, 2224–2248 (2006)

    Article  CAS  PubMed  Google Scholar 

  23. D. Gibellini, F. Vitone, P. Schiavone, C. Ponti, M.L. Placa, M.C. Re, Quantitative detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA in peripheral blood mononuclear cells by SYBR green real-time PCR technique. J. Clin. Virol. 29, 282 (2004)

    Article  CAS  PubMed  Google Scholar 

  24. J.R. Lakowicz, Principles of Fluorescence Spectroscopy, 3rd edn. (Springer, New York, 2006)

    Book  Google Scholar 

  25. M.-M. Wu, L.-Y. Zhang, Y.-H. Qin, Z.-N. Chen, Bis[μ-bis(diphenylphosphino)methane-κ2P:P′]bis[diacetonitrilecopper(I)] bis(hexafluorophosphate). Acta Cryst. Sect. E 59, m195–m196 (2003)

    Article  CAS  Google Scholar 

  26. B.A. Babgi, J.H. Alsayari, B. Davaasuren, A.-H.M. Emwas, M. Jaremko, M.H. Abdellattif, M.A. Hussien, Synthesis, structural studies and anticancer properties of the [CuBr(PPh3)2(4,6-dimethyl-2-thiopyrimidine-κS]. Crystals 11, 688 (2021)

    Article  CAS  Google Scholar 

  27. S. Nafisi, G.B. Sadeghi, A. PanahYab, Interaction of aspirin and vitamin C with bovine serum albumin. J. Photochem. Photobiol. B: Biol. 105, 198–202 (2011)

    Article  CAS  Google Scholar 

  28. B.K. Hoefelschweiger, A. Duerkop, O.S. Wolfbeis, Novel type of general protein assay using a chromogenic and fluorogenic amine-reactive probe. Anal. Biochem. 344, 122–129 (2005)

    Article  CAS  PubMed  Google Scholar 

  29. I. Petitpas, A.A. Bhattacharya, S. Twine, M. East, S. Curryi, Crystal structure analysis of warfarin binding to human serum albumin: anatomy of drug site I. J. Biol. Chem. 276, 22804–22809 (2001)

    Article  CAS  PubMed  Google Scholar 

  30. N.D. Al-Khathami, K.S. Al-Rashdi, B.A. Babgi, M.A. Hussien, M.N. Arshad, N.E. Eltayeb, S.E. Elsilk, J. Lasri, A.S. Basaleh, M. Al-Jahdali, Spectroscopic and biological properties of platinum complexes derived from 2-pyridyl Schiff bases. J. Saudi Chem. Soc. 23, 903–915 (2019)

    Article  CAS  Google Scholar 

  31. M.H. Abdel-Rhman, M.A. Hussien, H.M. Mahmoud, N.M. Hosny, Synthesis, characterization, molecular docking and cytotoxicity studies on N-benzyl-2-isonicotinoylhydrazine-1-carbothioamide and its metal complexes. J. Mol. Struct. 1196, 417–428 (2019)

    Article  CAS  Google Scholar 

  32. J.C. Cole, C.W. Murray, J.W. Nissink, R.D. Taylor, R. Taylor, Comparing protein-ligand docking programs is difficult. Proteins 60, 325–332 (2005)

    Article  CAS  PubMed  Google Scholar 

  33. N. Muanza, B.W. Kim, K.L. Euler, L. Williams, Antibacterial and antifungal activities of nine medicinal plants from Zaire. Int. J. Pharmacogn. 32, 337–345 (1994)

    Article  Google Scholar 

  34. J.M. Pezzuto, C.-T. Che, D.D. McPherson, J.-P. Zhu, G. Topcu, C.A.J. Erdelmeier, G.A. Cordell, DNA as an affinity probe useful in the detection and isolation of biologically active natural products. J. Nat. Prod. 54, 1522–1530 (1991)

    Article  CAS  PubMed  Google Scholar 

  35. P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J. Warren, H. Bokesch, S. Kenney, M. Boyd, New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107–1112 (1990)

    Article  CAS  PubMed  Google Scholar 

  36. A. Kaeser, M. Mohankumar, J. Mohanraj, F. Monti, M. Holler, J.-J. Cid, O. Moudam, I. Nierengarten, L. Karmazin-Brelot, C. Duhayon, B. Delavaux-Nicot, N. Armaroli, J.-F. Nierengarten, Heteroleptic copper(I) complexes prepared from phenanthroline and bis-phosphine ligands. Inorg. Chem. 52, 12140–12151 (2013)

    Article  CAS  PubMed  Google Scholar 

  37. S. Roy, T.K. Mondal, P. Mitra, C. Sinha, Copper(I)/silver(I)-phosphine-N-{(2-pyridyl)methyliden}-6-coumarin complexes: syntheses, structures, redox interconversion, photophysical properties and DFT computation. Polyhedron 51, 27–40 (2013)

    Article  CAS  Google Scholar 

  38. S. Al-Harthi, J.I. Lachowicz, M.E. Nowakowski, M. Jaremko, Ł Jaremko, Towards the functional high-resolution coordination chemistry of blood plasma human serum albumin. J. Inorg. Biochem. 198, 110716 (2019)

    Article  CAS  PubMed  Google Scholar 

  39. M.K. Helms, C.E. Petersen, N.V. Bhagavan, D.M. Jameson, Time-resolved fluorescence studies on site-directed mutants of human serum albumin. FEBS Lett. 408, 67–70 (1997)

    Article  CAS  PubMed  Google Scholar 

  40. M. El-Kemary, M. Gil, A. Douhal, Relaxation dynamics of piroxicam structures within human serum albumin protein. J. Med. Chem. 50, 2896–2902 (2007)

    Article  CAS  PubMed  Google Scholar 

  41. X.M. He, D.C. Carter, Atomic structure and chemistry of human serum albumin. Nature 358, 209–215 (1992)

    Article  CAS  PubMed  Google Scholar 

  42. V. Lhiaubet-Vallet, Z. Sarabia, F. Boscá, M.A. Miranda, Human serum albumin-mediated stereodifferentiation in the triplet state behavior of (S)- and (R)-carprofen. J. Am. Chem. Soc. 126, 9538–9539 (2004)

    Article  CAS  PubMed  Google Scholar 

  43. D.P. Yeggoni, M. Gokara, D.M. Manidhar, A. Rachamallu, S. Nakka, C.S. Reddy, R. Subramanyam, Binding and molecular dynamics studies of 7-hydroxycoumarin derivatives with human serum albumin and its pharmacological importance. Mol. Pharm. 11, 1117–1131 (2014)

    Article  CAS  PubMed  Google Scholar 

  44. O. Exner, Calculating equilibrium constants from spectral data: reliability of the Benesi-Hildebrand method and its modifications. Chemomet. Intell. Lab. Syst. 39, 85–93 (1997)

    Article  CAS  Google Scholar 

  45. N. Shahabadi, S. Kashanian, K. Shalmashi, H. Roshanfekr, DNA interaction with PtCl2(LL) (LL = chelating diamine ligand: N, N-dimethyltrimethylendiamine) complex. Appl. Biochem. Biotechnol. 158, 1–10 (2009)

    Article  CAS  PubMed  Google Scholar 

  46. B. Bhattacharya, S. Nakka, L. Guruprasad, A. Samanta, Interaction of bovine serum albumin with dipolar molecules: fluorescence and molecular docking studies. J. Phys. Chem. B 113, 2143–2150 (2009)

    Article  CAS  PubMed  Google Scholar 

  47. S. Dasari, P.B. Tchounwou, Cisplatin in cancer therapy: molecular mechanisms of action. Eur. J. Pharm. 740, 364–378 (2014)

    Article  CAS  Google Scholar 

  48. V.L. Goodman, E.P. Rock, R. Dagher, R.P. Ramchandani, S. Abraham, J.V.S. Gobburu, B.P. Booth, S.L. Verbois, D.E. Morse, C.Y. Liang, N. Chidambaram, J.X. Jiang, S. Tang, K. Mahjoob, R. Justice, R. Pazdur, Approval summary: sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 13, 1367–1373 (2007)

    Article  CAS  PubMed  Google Scholar 

  49. B.A. Babgi, D. Domyati, M.H. Abdellattif, M.A. Hussien, Evaluation of the anticancer and DNA-binding characteristics of dichloro (diimine) zinc (II) complexes. Chemistry 3, 1178–1188 (2021)

    Article  CAS  Google Scholar 

  50. R.J. Motzer, B. Escudier, A. Gannon, R.A. Figlin, Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma. Oncologist 22, 41–52 (2017)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under grant no. (G-1436-130-43). The authors, therefore, acknowledge with thanks DSR technical and financial support.

Funding

This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia under Grant No. (G-1436-130-43). The authors, therefore, acknowledge with thanks DSR technical and financial support.

Author information

Author notes

  1. Bandar A. Babgi and Najah A. Alzaidi contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia

    Bandar A. Babgi, Najah A. Alzaidi, Jalal H. Alsayari, Mutlaq Aljahdali & Mostafa A. Hussien

  2. Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia

    Abdul-Hamid M. Emwas

  3. Division of Biological and Environmental Sciences and Engineering (BESE), Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia

    Mariusz Jaremko

  4. Chemistry Department, Deanship of Scientific Research, College of Sciences, Taif University, Al-Haweiah, P.O. Box 11099, Taif, 21944, Saudi Arabia

    Magda H. Abdellattif

  5. Department of Chemistry, Faculty of Science, Port Said University, Port Said, 42521, Egypt

    Mostafa A. Hussien

Authors
  1. Bandar A. Babgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Najah A. Alzaidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jalal H. Alsayari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdul-Hamid M. Emwas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mariusz Jaremko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Magda H. Abdellattif
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mutlaq Aljahdali
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mostafa A. Hussien
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, BAB; Data curation, NAA and JHA; Formal analysis, JHA, MHA, A-HME and MJ; Funding acquisition, BAB; Investigation, BAB and NAA; Methodology, A-HME; Project administration, BAB; Resources, MJ and BAB; Software, MHA and MAH; Supervision, BAB; Visualization, MAH; Writing–original draft, BAB; Writing–review & editing, BAB and MA.

Corresponding author

Correspondence to Bandar A. Babgi.

Ethics declarations

Conflict of interest

The authors decalre that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 5973 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Babgi, B.A., Alzaidi, N.A., Alsayari, J.H. et al. Synthesis, HSA-Binding and Anticancer Properties of [Cu2(\(\mu\)-dppm)2(N^N)2]2+. J Inorg Organomet Polym 32, 4005–4013 (2022). https://doi.org/10.1007/s10904-022-02404-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10904-022-02404-y

Keywords

Search

Navigation