DNA/HSA Interactions and Anticancer Activity of a Palladium(II) Saccharinate Complex Bearing Ethyldiphenylphosphine

Abstract

The binding interactions of cis-[Pd(sac)2(PPh2Et)2] with DNA and HSA were comprehensively studied by a number of experimental methods and molecular docking studies. The Pd(II) complex bound to AT-rich sites in the major groove of DNA, and interacted with the hydrophobic cavity of the subdomain IIA of HSA. These experimental findings were supported by molecular docking studies. The Pd(II) complex had shown strong cytotoxic activity against different cancer cell lines and it also had selectivity especially for MCF-7 breast cancer cells higher than cisplatin.

Keywords

• Paladyum(II)
• Sakkarinat
• Antikansr aktivite
• DNA/HSA bağlanma

Thanks

The assistance of Dr. Buse Cevatemre (Koç Üniversity) in the cytotoxicity experiments is greatly acknowledged.

References

1. 1. A. Garoufis, S.K. Hadjikakou, N. Hadjiliadis, Palladium coordination compounds as anti-viral, anti-fungal, anti-microbial and anti-tumor agents Coord. Chem. Rev., 253 (2009) 1384-1397.
2. 2. Md N. Alam, F. Huq, Comprehensive review on tumour active palladium compounds and structure–activity relationships, Coord. Chem. Rev., 316 (2016) 36-67.
3. 3. E.Z. Jahromi, A. Divsalar, A.A. Saboury, S. Khaleghizadeh, H. Mansouri‑Torshizi, I. Kostova, Palladium complexes: new candidates for anti‑cancer drugs, J. Iran Chem Soc., 13 (2016) 967-989.
4. 4. T. Lazarevic, A. Rilak, Z.D. Bugarcic, Platinum, palladium, gold and ruthenium complexes as anticancer agents: Current clinical uses, cytotoxicity studies and future perspectives, Eur. J. Med. Chem., 142 (2017) 8-31.
5. 5. E.J. Baran, V.T. Yilmaz, Metal complexes of saccharin, Coord. Chem. Rev., 250 (2006) 1980-1999.
6. 6. M. Cavicchioli, A.C. Massabni, E.E. Castellano, L.P.B. Sabeh, C.M. Costa-Neto, Synthesis and X-ray structure of the dinuclear platinum(II) complex with saccharin {K[Pt(sac)3(H2O)]•H2O}2: studies on its antiproliferative activity in aqueous solution, Inorg. Chim. Acta. 360 (2007) 3055-3060.
7. 7. E. Ulukaya, F. Ari, K. Dimas, M. Sarimahmut, E. Guney, N. Sakellaridis, V.T. Yilmaz, Cell death-inducing effect of novel palladium(II) and platinum(II) complexes on non-small Cell lung cancer cells in vitro, J. Cancer Res. Clin. Oncol., 137 (2011)1425-1434.
8. 8. E. Ulukaya, F. Ari, K. Dimas, E.I. Ikitimur, E. Guney, V.T. Yilmaz, Anti-cancer activity of a novel palladium(II) complex on human breast cancer cells in vitro and in vivo, Eur. J. Med. Chem., 46 (2011) 4957-4963.

9. 9. E. Guney, V.T. Yilmaz, F. Ari, O. Buyukgungor, E. Ulukaya, Synthesis, characterization, structures and cytotoxic activity of palladium(II) and platinum(II) complexes containing bis(2-pyridylmethyl)amine and saccharinate, Polyhedron 30 (2011) 114-122.
10. 10. F. Ari, N. Aztopal, C. Icsel, V.T. Yilmaz, E. Guney, O. Buyukgungor, E. Ulukaya, Synthesis, structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro, Bioorg. Med. Chem., 21 (2013) 6427-6434.
11. 11. S.A. Al-Jibori, G.H. Al-Jibori, L.J. Al-Hayaly, C. Wagner, H. Schmidt, S. Timur, F.B. Barlas, E. Subasi, S. Ghosh, G. Hogarth, Combining anti-cancer drugs with artificial sweeteners: synthesis and anti-cancer activity of saccharinate (sac) and thiosaccharinate (tsac) complexes cis-[Pt(sac)2(NH3)2] and cis-[Pt(tsac)2(NH3)2], J. Inorg. Biochem., 141 (2014) 55-57.
12. 12. V.T. Yilmaz, C. Icsel, O.R. Turgut, M. Aygun, M. Erkisa, M.H. Turkdemir, E. Ulukaya, Synthesis, structures and anticancer potentials of platinum(II) saccharinate complexes of tertiary phosphines with phenyl and cyclohexyl groups targeting mitochondria and DNA, Eur. J. Med. Chem., 155 (2018) 609-622.
13. 13. C. Icsel, V.T. Yilmaz, M. Aygun, B. Cevatemre, P. Alper, E. Ulukaya, Palladium(II) and platinum(II) saccharinate complexes with bis(diphenylphosphino)methane /ethane: synthesis. S-phase arrest and ROS-mediated apoptosis in human colon cancer cells, Dalton Trans., 47 (2018) 11397-11410.
14. 14. V.T. Yilmaz, C. Icsel, M. Aygun, M. Erkisa, E. Ulukaya, Pd(II) and Pt(II) saccharinate complexes of bis(diphenylphosphino)propane/butane: Synthesis, structures, antiproliferative activity and mechanism of action, Eur. J. Med. Chem., 158 (2018) 534-547.
15. 15. C. Icsel, V.T. Yilmaz, B. Cevatemre, M. Aygun, E. Ulukaya, Structures and anticancer activity of chlorido platinum(II) saccharinate complexes with mono- and dialkylphenylphosphines, J. Inorg. Biochem., 195 (2019) 39-50.
16. 16. C. Icsel, V.T. Yilmaz, B. Cevatemre, M. Aygun, E. Ulukaya, Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress‑induced apoptosis, J. Biol. Inorg. Chem., 25 (2020) 75-87.
17. 17. C. Icsel, V.T. Yılmaz, M. Aygün, E. Ulukaya, Trans-Pd/Pt(II) saccharinate complexes with a phosphine ligand: Synthesis, cytotoxicity and structure-activity relationship, Bioorg. Med. Chem. Lett., 30 (2020) 127077.
18. 18. C. Icsel, V.T. Yilmaz, B. Cevatemre, M. Aygun, E. Ulukaya, Cytotoxic platinum(II) complexes derived from saccharinate and phosphine ligands: synthesis, structures, DNA cleavage, and oxidative stress‑induced apoptosis, J. Biol. Inorg. Chem., 25 (2020) 75-87.
19. 19. V.T. Yilmaz, C. Icsel, O.R. Turgut, M. Aygun, E. Evren, I. Ozdemir, Synthesis, structures and catalytic activity of Pd(II) saccharinate complexes with monophosphines in direct arylation of five-membered heteroarenes with aryl bromides, Inorg. Chim. Acta, 500 (2020) 119220.
20. 20. H.A. Benesi, J.H. Hildebrand, A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons, J. Am. Chem. Soc., 71 (1949) 2703-2707.
21. 21. O. Stern, M. Volmer, Über die abklingzeit der fluoreszenz, Z. Physik., 20 (1919) 183-188.
22. 22. J. Min, X.M. Meng-Xia, Z. Dong, L. Yuan, L. Xiao-Yu, C. Xing, Spectroscopic studies on the interaction of cinnamic acid and its hydroxyl derivatives with human serum albumin, J. Mol. Struct., 692 (2004) 71-80.
23. 23. O. Trott, A.J. Olson, Autodock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, J. Comput. Chem., 31 (2010) 455-461.
24. 24. D. Suh, J.B. Chaires, Criteria for the mode of binding of DNA binding agents, Bioorg. Med. Chem., 3 (1995) 723-728.
25. 25. Q. Jiang, N. Xiao, P. Shi, Y. Zhu, Z. Guo, Design of artificial metallonucleases with oxidative mechanism, Coord. Chem. Rev., 251 (2007) 1951-1972.
26. 26. F. Mancin, P. Scrimin, P. Tecilla, U. Tonellato, Artificial metallonucleases, Chem. Commun., (2005) 2540–2548.
27. 27. N.E. Basken, C.J. Mathias, M.A. Green, Elucidation of the human serum albumin (HSA) binding site for the Cu-PTSM and Cu-ATSM radiopharmaceuticals. J. Pharm. Sci., 98 (2009) 2170-2179.
28. 28. P. Mandal, T. Ganguly, Fluorescence spectroscopic characterization of the interaction of human adult hemoglobin and two isatins, 1-methylisatin and 1-phenylisatin: a comparative study, J. Phys. Chem. B, 113 (2009) 14904-14913.
29. 29. D.C. Carter, J.X. Ho, Structure of serum albumin, Adv. Protein Chem., 45 (1994) 153-203.