Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin

• Published in: Journal of luminescence 2015-08, Vol.164, p.123-130
• Main Authors: Alam, Parvez, Chaturvedi, Sumit Kumar, Anwar, Tamanna, Siddiqi, Mohammad Khursheed, Ajmal, Mohd Rehan, Badr, Gamal, Mahmoud, Mohamed H., Hasan Khan, Rizwan
• Format: Article
• Language: English
• Subjects: Binding; Fluorescence quenching; Molecular docking; Serum albumin
• ISSN: 0022-2313; 1872-7883
• DOI: 10.1016/j.jlumin.2015.03.011

Interaction of pharmacologically important anticancer drug cytosine β-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 β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4×103M−1. The average binding distance between drug and Trp214 of HSA was found to be 2.23nm on the basis of the theory of Förster'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 (ΔH=−26.01kJmol−1 and TΔS=6.5kJmol−1) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-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 β-D arabinofuranoside with HSA and associated alterations. •Comprehensive insight into the interaction of CBDA with HSA.•The interaction process is spontaneous and exothermic.•The main governing forces for stabilizing HSA–CBDA complex are van der Waal interaction and hydrogen bonding.•CBDA binds at subdomain IB on HSA.