title: A biophysical and computational study unraveling the molecular interaction mechanism of a new Janus kinase inhibitor Tofacitinib with bovine serum albumin.
abstract: The interaction of a recently certified kinase inhibitor Tofacitinib (TFB) with bovine serum albumin (BSA) has been studied, by spectroscopic and molecular docking studies. Spectrofluorimetric measurements at 3 different temperatures (288, 298, and 310 K) showed that TFB quench the intrinsic fluorescence of BSA upon forming a nonfluorescent complex. The intrinsic fluorescence data showed that TFB binds to BSA with binding constant (Kb) of approximately 104M-1, affirming a significant affinity of TFB with BSA. The decrease in Stern-Volmer quenching constant with increasing temperature exhibited the static mechanism of quenching. Negative value of ΔG (-6.94 ± 0.32 kcal·mol-1), ΔH (-7.87 ± 0.52 kcal·mol-1), and ΔS (-3.14 ± 0.42 cal·mol-1·K-1) at all 3 temperatures declared the reaction between BSA and TFB to be spontaneous and exothermic. Far-UV circular dichroism spectroscopy results demonstrated an increase in helical content of BSA in the presence of TFB. Moreover, dynamic light scattering measurements showed that TFB resulted into a decrease in the hydrodynamic radii (from 3.6 ± 0.053 to 2.9 ± 0.02 nm) of BSA. Molecular docking studies confirmed that TFB binds near site II on BSA, hydrogen bonding, and hydrophobic interaction were involved in the BSA-TFB complex formation. The present study characterizing the BSA-TFB interaction could be significant towards gaining an insight into the drug pharmacokinetics and pharmacodynamics and also in the direction of rational drug designing with better competence, against emerging immune-mediated diseases, ie, alopecia and rheumatoid arthritis.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ali Saber
authors.initials: AS
authors.lastname: Abdelhameed
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Mohammad Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Syed Mohammad
authors.initials: SM
authors.lastname: Zakariya
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D002417:Cattle; D002942:Circular Dichroism; D000067493:Dynamic Light Scattering; D006860:Hydrogen Bonding; D000075242:Janus Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation / Q000379:methods*; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D000075242:Janus Kinase Inhibitors; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; D012710:Serum Albumin, Bovine; C479163:tofacitinib
keywords: binding constant; circular dichroism spectroscopy; dynamic light scattering; kinase inhibitor; molecular docking