title: Interplay of multiple interaction forces: Binding of tyrosine kinase inhibitor nintedanib with human serum albumin.
abstract: In this study, we have investigated the binding affinity of the newly approved tyrosine kinase inhibitor nintedanib (NIB) with human serum albumin under simulated physiological condition. The obtained results demonstrate that fluorescence intensity of human serum albumin (HSA) gets quenched by NIB and quenching occurs in static manner. Binding parameters calculated from modified Stern-Volmer equation shows that the drug binds to human serum albumin with a binding constant in the order of 10(3), with the number of binding sites approximately equal to one. Synchronous fluorescence data deciphered the change in the microenvironment of tryptophan (Trp) residue in HSA. Circular dichroism data showed an increase in helical content upon drug binding. Dynamic light scattering measurements deciphered the reduction in hydrodynamic radii of the protein, further differential scanning calorimetry results shows that nintedanib increase the thermostability of HSA. Molecular docking results demonstrated that major binding forces involved in the complex formation are hydrogen bonding and hydrophobic interaction.
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Abdelhameed
authors.affiliation: Recombinant Gene Product Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Ravi Kant
authors.initials: RK
authors.lastname: Rajpoot
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, India. Electronic address: rizwanhkhan@hotmail.com.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D012709:Serum Albumin; C530716:nintedanib
keywords: Binding; Docking; Fluorescence quenching; Serum albumin