title: A multitechnique approach to probe the interaction of a therapeutic tyrosine kinase inhibitor nintedanib and bovine serum albumin.
abstract: Drug and protein interaction provides a structural guideline in the rational drug designing and in the synthesis of new and improved drugs with greater efficacy. We have examined here the interaction tendency and mechanism of nintedanib (NTB), an anticancer drug (tyrosine kinase inhibitor) with bovine serum albumin (BSA), by spectroscopic techniques. The decline in Stern-Volmer quenching constants and binding constant with the temperature rise suggests that BSA forms a complex with NTB. Binding constant obtained by modified Stern-Volmer equation at 3 temperatures was realized to be of the order of ~104M-1. Negative ΔG (~-5.93 kcal mol-1), ΔH (-3.74 kcal mol-1), and ΔS (-1.50 kcal mol-1) values exhibited a spontaneous and exothermic reaction between BSA and NTB. NTB molecule interacts with BSA by forming hydrogen bonds, as elucidated by fluorescence results. Moreover, a minor increment in the helical conformation of BSA upon its binding to NTB was observed by circular dichroism spectroscopy. The modification in protein's symmetry and a decline in hydrodynamic radii were observed in the presence of NTB (from ~3.6 to ~3 nm) as obtained by the dynamic light scattering measurement results.
authors.affiliation: a 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: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh , Uttar Pradesh , India.
authors.forename: Saima
authors.initials: S
authors.lastname: Nusrat
authors.affiliation: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh , Uttar Pradesh , India.
authors.forename: Sanjhi
authors.initials: S
authors.lastname: Paliwal
authors.affiliation: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh , Uttar Pradesh , India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh , Uttar Pradesh , India.
authors.forename: Nida
authors.initials: N
authors.lastname: Zaidi
authors.affiliation: b Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh , Uttar Pradesh , India.
authors.forename: Rizwan Hasan
authors.identifier: http://orcid.org/0000-0002-9965-8982
authors.initials: RH
authors.lastname: Khan
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002942:Circular Dichroism; D000067493:Dynamic Light Scattering; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D012710:Serum Albumin, Bovine; D011505:Protein-Tyrosine Kinases; C530716:nintedanib
keywords: Binding constant; circular dichroism; quenching