Novel Pt(II) Complex and Its Pd(II) Aanalogue. Synthesis, Characterization, Cytotoxicity and DNA-interaction

Document Type: Article

Authors

1 Department of Chemistry, University of Zabol, Zabol

2 Department of Chemistry, University of Sistan & Baluchestan, Zahedan

3 Department of Biological Sciences, Kharazmi University, Tehran

4 Institute of Biochemistry and Biophysics, University of Tehran, Tehran

Abstract

The ability of small molecules to perturb the natural structure and dynamics of nucleic acids is intriguing and has potential applications in cancer therapeutics. This work reports the synthesis, characterization, cytotoxicity and DNA-binding studies of two cytotoxic and intercalative [M(bpy)(pyrr-dtc)]NO3 complexes (where M = Pt(II) and Pd(II), bpy = 2,2´-bipyridine and pyrr-dtc = pyrrolidinedithio-carbamate). Binding interaction of these complexes with calf thymus DNA (CT-DNA) was investigated by spectrophotometric, spectrofluorometric and gel filtration techniques. Gel filtration studies indicate that the binding of these complexes with CT-DNA is strong enough not to readily break. The binding constant and the thermodynamic parameters have been determined using absorption measurements. The fluorescence studies indicate that the two complexes bind to CT-DNA through an intercalative mode. The cytotoxic activity of these metal complexes has been tested against chronic myelocytic leukemia K562 cell lines and revealed much lower 50% cytotoxic concentration (Cc50) than that of cisplatin. We hope that such spectroscopic studies to be indeed helpful in studying the pharmacological response of drugs and design of dosage forms.

Graphical Abstract

Novel Pt(II) Complex and Its Pd(II) Aanalogue. Synthesis, Characterization, Cytotoxicity and DNA-interaction

Keywords

Main Subjects


[1]           A. Pasini, F. Zunino, Angew. Chem. Int. Ed. Engl. 26 (1987) 615.

[2]           N. Farrell, Y. Que, M.P. Hacker, J. Med. Chem. 33 (1990) 2179.

[3]           A.G. Sykes, Plat. Met. Rev. 32 (1988) 170.

[4]           S.E. Sherman, S. Lippard, J. Chem. Rev. 87 (1987) 1153.

[5]           E.J. Gao, L. Wang, M.C. Zhu, L. Liu, W.Z. Zhang, Eur. J. Med. Chem. 45 (2010) 311.

[6]           K.E. Erkkila, D.T. Odom, K.J. Barton, J. Chem. Rev. 99 (1999) 2777.

[7]           N. Farrell, Transition Metal Complexes as Drugs and Chemotherapeutic in: B.R. James, R. Ugo (Eds.), Catalysis by Metal Complexes, Kluwer, Dordrecht, 1989.

[8]           M. Cusumano, A. Giannetto, J. Inorg. Biochem. 65 (1997) 137.

[9]           C.M. Che, M. Yang, K.H. Wong, H.L. Chan, W. Lam, Chem. Eur. J. 5 (1999) 3350.

[10]       M. Cusumano, M.L. Di Pietro, A. Giannetto, F. Nicolo, E. Rotondo, Inorg. Chem. 37 (1998) 563.

[11]       S. Hidaka, M. Tsuruoka, T. Funakoshi, H. Shimada, M. Kiyozumi, S. Kojima, Ren. Fail. 16 (1994) 337.

[12]       D.L. Bodenner, P.C. Dedon, P.C. Keng, R. Borch, Cancer Res. 46 (1986) 2745.

[13]       A. Trevisan, C. Marzano, P. Cristofori, M.B. Venturini, L. Giovagnini, D. Fregona, Arch. Toxicol. 76 (2002) 262.

[14]       R. Mital, N. Jain, T.S. Srivastava, J. Inorg. Chim. Acta 166 (1989) 135.

[15]       A.I. Vogel, In A Textbook of Practical Organic Chemistry; 3rd ed.; Longman Scientific & Technical, 1989.

[16]       F.A. Palocsay, J.V. Rund, Inorg. Chem. 8 (1969) 524.

[17]       D.C. Menezes, F.T. Vieira, G.M. de-Lima, A.O. Porto, M.E. Cortés, J.D. Ardisson, T.E. Albrecht-Schmitt, Eur. J. Med. Chem. 45 (2005) 1277.

[18]       L. Ronconi, L. Giovagnini, C. Marzano, et al., Inorg. Chem. 44 (2005) 1867.

[19]       A. Manohar, K. Ramalingam, G. Bocelli, L. Righi, Inorg. Chim. Acta 314 (2001) 177.

[20]       L. Kumar, N.R. Kandasamy, T.S. Srivastava, A.J. Amonkar, M.K. Adwankar, M.P. Chitnis, J. Inorg. Biochem. 23 (1984) 1.

[21]       W.J. Gearg, Coord. Chem. Rev. 7 (1971) 81.

[22]       A. Divsalar, A.A. Saboury, R. Yousefi, A.A. Moosavi-Movahedi, H. Mansoori-Movahedi, H. Mansouri-Torshizi, Int. J. Biol. Macromol.  40 (2007) 381.

[23]       M. Saeidfar, H. Mansouri-Torshizi, G.R. Behbehani, A.A. Saboury, A. Divsalar, B. Kor. Chem. Soc. 30 (2009) 1951.

[24]       M. Islami-Moghaddam, H. Mansouri-Torshizi, A. Divsalar, A.A. Saboury, J. Iran. Chem. Soc. 6 (2009) 552.

[25]       S. Satyanarayana, J.C. Dabrowiak, J.B. Chaires, Biochemistry 31 (1992) 9319.

[26]       H. Mansouri-Torshizi, M. Islami-Moghaddam, A. Divsalar, A.A. Saboury, Acta Chim. Slov. 58 (2011) 811.

[27]       M.F. Reichmann, S.A. Rice, C.A. Thomas, P. Doty, J. Am. Chem. Soc. 76 (1954) 3047.

[28]       Z.H. Xu, F.J. Chen, P.X. Xi, X.H. Liu, Z.Z. Zeng, J. Photochem. Photobiol. A Chem. 196 (2008) 77.

[29]       S.Z. Bathaie, A. Bolhasani, R. Hoshyar, B. Ranjbar, F. Sabouni, A.A. Moosavi-Movahedi, DNA Cell Biol. 26 (2007) 533

[30]       L. Peres-Flores, A.J. Ruiz-Chica, J.G. Delcros, F.M. Sanches, F. Ramirez, J. Spectrochim. Acta A 69 (2008) 1089.

[31]       R.F. Greene, C.N. Pace, J. Biol. Chem. 249 (1974) 5388.

[32]       A.M.Q. King, B.H. Nicholson, Biochem. J. 114 (1969) 679.

[33]       M. Ghadermarzi, A.A. Saboury, A.A. Moosavi-Movahedi, Polish J. Chem. 72 (1998) 2024.

[34]       A.A. Saboury, A.K. Bordbar, A.A. Moosavi-Movahedi, B. Chem. Soc. JPN. 69 (1996) 3031.

[35]       G.M. Barrow, Physical Chemistry of the Life Sciences, in Physical Chemistry, Graw-Hill, New York, 1988.

[36]       H. Mansouri-Torshizi, M. Saeidifar, A. Divsalar, A.A. Saboury, J. Biomol. Struct. Dyn. 28 (2011) 805.

[37]       A.A. Saboury, J. Iran. Chem. Soc. 3 (2006) 1. 

[38]       M.L. James, G.M. Smith, J.C. Wolford, Applied Numerical Methods for Digital Computer, New York, Harper and Row Publisher, 1985.

[39]       M.P. Hacker, E.B. Douple, I.H. Krakoff, in: M.A. Nijhoff (Ed.), Platinum Coordination Complexes in Cancer Chemotherapy, Boston, 1984.

[40]       H. Mansouri-Torshizi, M. Islami-Moghaddam, A.A. Saboury, Acta Biochim. Biophys. Sin. 35 (2003) 886.

[41]       V.A. Izumrudov, M.V. Zhiryakova, A.A. Goulko, Langmuir 18 (2002) 10348.

[42]       B.C. Baguley, M. LeBret, Biochemistry 23 (1984) 937.

[43]       J.R. Lakowicz, G. Webber, Biochemistry 12 (1973) 4161.

[44]       M. Howe-Grant, K.C. Wu, W.R. Bauer, S.J. Lippard, Biochemistry 15 (1976) 4339.

[45]       H. Mansouri-Torshizi, T.S. Srivastava, H.K. Parekh, M.P. Chitnis, J. Inorg. Biochem. 45 (1992) 135.

[46]       H. Mansouri-Torshizi, R. Mital, T.S. Srivastava, H. Parekh, M. P. Chitnis, J. Inorg. Biochem. 44 (1991) 239.