title: Binding of Janus kinase inhibitor tofacitinib with human serum albumin: multi-technique approach.
abstract: In this report, we have investigated the binding affinity of tofacitinib with human serum albumin (HSA) under simulated physiological conditions by using UV-visible spectroscopy, fluorescence quenching measurements, dynamic light scattering (DLS), differential scanning calorimetry (DSC) and molecular docking methods. The obtained results demonstrate that fluorescence intensity of HSA gets quenched by tofacitinib and quenching occurs in static manner. Binding parameters calculated from modified Stern-Volmer equation shows that the drug binds to HSA with a binding constant in the order of 10(5). Synchronous fluorescence data deciphered the change in the microenvironment of tryptophan residue in HSA. UV spectroscopy and DLS measurements deciphered complex formation and reduction in hydrodynamic radii of the protein, respectively. Further DSC results show that tofacitinib increases the thermo stability of HSA. Hydrogen bonding and hydrophobic interaction are the main binding forces between HSA and tofacitinib as revealed by docking results.
authors.affiliation: a 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: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D012709:Serum Albumin; C479163:tofacitinib; D053612:Janus Kinases
keywords: binding; fluorescence quenching; molecular docking; serum albumin