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Effect of Presence of Aliphatic Glycine in the Anti-cancer Platinum Complex Structure on Human Serum Albumin Binding

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Abstract

Purpose

In this work, a new water-soluble Pt(II) complex was synthesized with aliphatic glycine ligand with a formula of cis-[Pt(NH3)2(isopentylgly)]NO3, as an anti-cancer drug, and characterized. To determine the binding constant of the human serum albumin (HSA, the most abundant carrier proteins in the human circulatory system) to this complex and the binding site of the complex on HSA, the melting point of HSA and the kinetics of this interaction were investigated to introduce an anti-breast cancer drug with fewer side effects.

Methods

HSA interaction with the complex was studied via a spectroscopic method at 27 and 37 °C and physiological situation (I = 10 mM, pH = 7.4) and molecular docking.

Results

The toxicity value of this complex was obtained against the human cancer breast cell line of MCF-7. The thermodynamic parameters of enthalpy and entropy were also achieved in the empirical procedure. Due to the spontaneity of the interaction, Gibbs free energy variation was obtained negative. The binding constant of this complex to HSA was 3.9 × 105 (M−1). Empirical results showed that the quenching mechanism was static. Hill coefficients, Hill constant, complex aggregation number around protein, number of binding sites, and protein melting temperature with complex were obtained. The kinetics of this interaction was also investigated, which showed that this interaction follows a second-order kinetic. The molecular docking data indicated that the position of the interaction of complex on the protein was the site I in the sub-second IIA. Also, the hydrogen bonding and the hydrophobic interaction as the dominant binding forces were seen in complex–HSA formation.

Conclusion

This interaction with positive cooperativity was recognized via a superior hydrogen bond. The reasonable binding constant was also obtained, which could ultimately be a good option as an anti–breast cancer drug.

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Abbreviations

HSA:

Human serum albumin

PDB:

Protein Data Bank

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Acknowledgments

The authors of this article would like to thank the Payame Noor University of Isfahan.

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Authors and Affiliations

  1. Department of Chemistry, Payame Noor University (PNU), P.O BOX 19395-4697, Tehran, Iran

    Afrooz Shiekhzadeh, Nasrin Sohrabi & Mohsen Oftadeh

  2. Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran

    Mahboube Eslami Moghadam

  3. Department of cell & molecular biology, Faculty of Biological Sciences, Karazmi University, Tehran, Iran

    Adeleh Divsalar

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  1. Afrooz Shiekhzadeh
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  2. Nasrin Sohrabi
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  3. Mahboube Eslami Moghadam
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Correspondence to Nasrin Sohrabi or Mahboube Eslami Moghadam.

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Shiekhzadeh, A., Sohrabi, N., Eslami Moghadam, M. et al. Effect of Presence of Aliphatic Glycine in the Anti-cancer Platinum Complex Structure on Human Serum Albumin Binding. J Pharm Innov 17, 353–365 (2022). https://doi.org/10.1007/s12247-020-09508-3

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