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Multi-spectroscopic and HPLC Studies of the Interaction Between Estradiol and Cyclophosphamide With Human Serum Albumin: Binary and Ternary Systems

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Abstract

Drug resistance is a phenomenon that frequently impairs a proper treatment of infections and cancer with chemotherapy. Multidrug efflux transporters extrude structurally dissimilar organic compounds often providing resistance to multiple toxic chemotherapeutic agents. The quantitative analysis of drug efflux requires measuring the affinity of ligands. In this work, the interaction between cyclophosphamide (Cyc) and estradiol (ES) with human serum albumin (HSA) was studied by fluorescence polarization, circular dichroism and high-performance liquid chromatography (HPLC) under physiological conditions (pH = 7.4). Gradual addition of HSA led to a marked increase in fluorescence polarization. Our assays indicated that the protein was bound to these drugs with different K d. Also, the Hill coefficient showed a simple drug binding process with no cooperativity. Circular dichroism results revealed the occurrence of conformational changes in HSA molecules by the binding of Cyc and ES. The protein binding of the drug was studied by HPLC. Our results indicated that the drug was bound to the protein and that the presence of a second drug affected the interaction and resistance between the first drug and the protein.

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Acknowledgements

The financial support of the Research Council of the Mashhad Branch, Islamic Azad University is gratefully acknowledged. The authors also thank Dr. Ljungberg for the English editing.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Faculty of Sciences, Mashhad Branch, Islamic Azad University, Mashhad, Iran

    Zahra Sharif-Barfeh, Somaye Marouzi, Atena Sharifi Rad & Jamshidkhan Chamani

  2. Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran

    Ahmad Asoodeh

  3. Endoscopic and Minimally, Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Sima Beigoli

Authors
  1. Zahra Sharif-Barfeh
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  2. Sima Beigoli
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  3. Somaye Marouzi
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  4. Atena Sharifi Rad
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  5. Ahmad Asoodeh
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  6. Jamshidkhan Chamani
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Correspondence to Jamshidkhan Chamani.

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Sharif-Barfeh, Z., Beigoli, S., Marouzi, S. et al. Multi-spectroscopic and HPLC Studies of the Interaction Between Estradiol and Cyclophosphamide With Human Serum Albumin: Binary and Ternary Systems. J Solution Chem 46, 488–504 (2017). https://doi.org/10.1007/s10953-017-0590-2

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  • DOI: https://doi.org/10.1007/s10953-017-0590-2

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