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 10⁵. 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.

Keywords:

• serum albumin
• binding
• fluorescence quenching
• molecular docking

Acknowledgements

Facilities provided by IBU, Aligarh Muslim University, Aligarh are gratefully acknowledged. P.A. is grateful to Council of Scientific and Industrial Research, New Delhi, India for providing fellowship in the form of JRF. The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this Research Group No. RG-1435-025. Authors are also thankful to anonymous reviewers for critically review our manuscript and help us to raise scientific standard of our work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Deanship of Scientific Research at King Saud University [research group number RG-1435-025].