Title
Multi-spectroscopic and HPLC Studies of the Interaction Between Estradiol and Cyclophosphamide With Human Serum Albumin: Binary and Ternary Systems
Author
Zahra Sharif-Barfeh, Sima Beigoli, Somaye Marouzi, Atena Sharifi Rad, Ahmad Asoodeh, Jamshidkhan Chamani
Year
2017
Journal
Journal of Solution Chemistry
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 Kd. 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.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Ligand binding, Biochemistry