A structural study on the interaction of the anti-cancer compound of Platinum complex with human serum albumin

Noorizadeh, Sara; Divsalar, Adeleh; Eslami-Moghaddam, Mahbubeh; Saboury, Ali Akbar

doi:10.21859/acadpub.nbr.2.4.250

A structural study on the interaction of the anti-cancer compound of Platinum complex with human serum albumin

Authors

Sara Noorizadeh ¹

Adeleh Divsalar ¹

Mahbubeh Eslami-Moghaddam ²

Ali Akbar Saboury ³

¹ Department of Cell and Molecular Sciences, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

² Chemistry and Engineer Chemistry Research Center, Tehran, Iran

³ Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

https://doi.org/10.21859/acadpub.nbr.2.4.250

Abstract

Human serum albumin (HSA) is the most abundant protein in blood plasma, which is responsible for 80% of blood pressure; it also acts as a carrier protein for many compounds in the blood such as drugs. In the present study, the interaction and side-effects of a newly-designed anti-cancer compound of isopentyl-glycine1, 10-phenanthroline Platinum nitrate on HSA have been investigated. In this investigation, the side effects, values of the number of binding sites and the association binding constants of new synthesized Pt(II) complex have been studied by different spectroscopic (fluorescence and circular diachronic (CD) techniques at different temperatures of 25 and 37 °C. The analysis of fluorescence spectra showed that the addition of the complex led to a significant reduction in the fluorescence spectra of HSA via quenching mechanism. Also, it can change the three-dimensional structure of tryptophan existing in the protein. The number of binding sites, the Stern-Volmer quenching constant and the association constant of the complex were calculated on the HSA protein. The analysis of circular dichroic spectra showed that the complex can change the regular secondary structure of the protein via reduction of α helical structure and increase of β sheet structure which indicates a decrease in the stability of the protein. According to the results obtained, it can be concluded that this new synthesized Pt(II) complex can bind to the main blood carrier protein (HSA) and change the secondary and tertiary structure of the protein which can be considered as the side-effects of this drug.

Keywords

HSA

platinum complex

fluorescence

side effects

Thermodynamic parameters

20.1001.1.24236330.1394.2.4.2.5

Ascnzi, P. and Fasano, M. 2010. Allostery in a monomeric protein: The case of human serum albumin. – Biophysical Chemistry 148: 16-22.
Asha, J.M., Selvaraj, S., Paramaguru, G., Venuvanalingam, P. and Renganathan, R. 2011. Spectroscopic and molecular docking investigations on the intraction of Rutin with bovine serum albumin. – Zeitschrift Fur Physikalische Chemie. 225: 441-454.
Bertucci, C. and Domenici, E. 2002. Reversible and covalent binding of drugs to human serum albumin. Methodological approaches and physiological relevance. – Curr. Med. Chem. 9: 1463-1481.

Divsalar, A., Saboury, A.A., Ahadi, L., Zemanatiyar, E. and Mansouri-Torshizi, H. 2010. Investigation of effects of newly synthesized Pt(II) complex against human serum albumin and leukemia cell line of K562. BMB Reports 43: 766-771.
Divsalar, A., Bagheri, M.J., Saboury, A.A., Mansoori-Torshizi, H. and Amani, M. 2009. Investigation on the intraction of newly designed anticancer Pd(II) complexes with different aliphatic tails and human serum albumin. – J. Phys. Chem. B. 113: 14035-14042.
Giovagnini, L., Marzano, C., Bettio, F. and Fregona, D. 2005. Chemical and biological profiles of novel copper (II) complexes containing S-Donor ligands for the treatment of cancer. – J. Inorg. Biochem. 99: 21-39.
Han, X., Sun, J., Wang, Y. and He, Z. 2015. Recent advances in platinum (IV) complex-based delivery systems to improve Platinum (II) anticancer therapy. – Med. Res. Rev. 35: 68-99.
Ho, J.W. 2006. Potential and cytotoxicity of cis-platinum complex with antitumor activity in combination therapy. – Recent. Patent. Anti-cancer Drug Discovery 1: 129-134.
Iglesias, B.A., Barata, J.F., and Pereira, P.M. 2015. New platinum (II)-bipyridyl corrole complexes: Synthesis, characterization and binding studies with DNA and HSA. – J. Inorg. Biochem. 153: 32-41.
Knoll, J.D. and Turro, C. 2015. Control and utilization of ruthenium and rhodium metal complex excited states forphotoactivated cancer therapy. –Coord. Chem. Rev. 282: 110-126.
Kragh-Hansen, U. 1990. Structure and ligand binding properties of human serum albumin. – Dan-Med-Bull. 37: 57-84.
Lebwohl, D. and Canetta, R. 1998. Clinical development of platinum complexes in cancer therapy. – Europe Journal Cancer 34: 1522-1534.
Mansouri-Torshizi, H., Srivastava, T.S., Perekh, H.K. and Chitnis, M.P. 1992. Synthesis, spectroscopic, cytotoxic, and DNA binding studies of binuclear 2,2'-bipyridine-platinum(II) and-palladium(II) complexes of meso- alpha, alpha' –diaminoa -dipic and meso alpa, alpha'-diaminosuberic acids. – J. Inorg. Biochem. 45: 135-148.
Miklášová, N., Fischer-Fodor, E., Lönnecke, P., Ionuţ Tomuleasa, C., Virag, P., Perde Schrepler, M., Mikláš, P., Silaghi Dumitrescu, L. and Hey-Hawkins, E. 2012. Antiproliferative effect of novel platinum (II) and palladium (II) complexes on hepatic tumor stem cells in vitro. – Eur. J. Med. Chem. 4: 41-47.
Rosenberg, B., Van Kamp, L., Trosko, J.E. and Mansour, V.H. 1996. Platinium compounds: a new class of potent anti-tumor agents. – Nature 222: 385-386.
Sabin, H. and Sadler, J. 2009. Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs. – Drug Discovery Today 14: 23-24.
Shi, H., Cheng, Q., Yuan, S., Ding, X., Liu Y. 2015. Human serum albumin conjugated nanoparticles for pH and Redox-responsive delivery of a prodrug of Cisplatin. – Chemistry J. 46: 9-21.
Wang, K., Lu, J.F. and Li, R.C. 1996. The events that occur when Cisplatin encounters cells. – Coord. Chem. Rev. 151: 53-88.
Zhang, Q., Zhong, W., Xing, B., Tang, W. and Chen, Y. 1998. Binding properties and stoichiometries of a palla-dium(II) complex to metallothioneins in vivo and in vitro. – J. Inorg. Biochem. 72: 195-200.