Abstract
Interaction of pharmacologically important anticancer drug cytosine beta-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine beta-D arabinofuranoside interacts With HSA through static quenching mechanism with binding affinity of 2.4 x 10(3) M-1. The average binding distance between drug and Trp(214) of HSA was found to be 2.23 nm on the basis of the theory of Forster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV-visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (Delta H=-26.01 kJ mol(-1) and T Delta S=6.5 kJ mol(-1)) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine beta-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine beta-D arabinofuranoside with HSA and associated alterations. (C) 2015 Elsevier B.V. All rights reserved.