Spectrophotometric and molecular modelling studies on in vitro interaction of tyrosine kinase inhibitor linifanib with bovine serum albumin

Abstract

Linifanib (LNF) possess antitumor activity and acts by inhibiting receptor tyrosine kinase VEGF and PDGF. The interaction of BSA with the drug can provide valuable information regarding the pharmacokinetic and pharmacodynamics behavior of drug. In our study the spectrophotometric methods and molecular docking studies were executed to understand the interaction behavior of BSA and LNF. BSA has an intrinsic fluorescence and that fluorescence was quenched by LNF. This quenching process was studied at three different temperatures of 288, 300and 308 K. The interaction between LNF and BSA was due to static quenching because the Ksv (Stern-Volmer constant) at 288 K was higher than at 300 and 308 K. Kq (quenching rate constant) behaved in a similar fashion as the Ksv. Several other parameters like binding constants, number of binding sites and binding energy in addition to molecular docking studies were also used to evaluate the interaction process. A decrease in the binding constants was observed with increasing temperatures and the binding site number approximated unity. The decreasing binding constant indicates LNF–BSA complex stability. The site mark competition experiment confirmed the binding site for LNF was located on site II of BSA. UV–visible studies along with synchronous fluorescence confirm a small change in the conformation of BSA upon interaction with LNF. The thermodynamic analysis provided the values for free energy ΔG0, ΔH0 and ΔS0. The ΔG0 at the 288, 300 and 308 K ranged in between -21.5 to -23.3 kJ mol-1, whereas the calculated values of ΔH (-55.91 kJ mol-1) and ΔS0 (-111.74 J mol-1·K-1). The experimental and molecular docking results suggest that the interaction between LNF and BSA was spontaneous and they exhibited hydrogen bonding and van der Waals force between them.

Evaluation of Biophysical Interaction between Newly Synthesized Pyrazoline Pyridazine Derivative and Bovine Serum Albumin by Spectroscopic and Molecular Docking Studies

“…Spectroscopy. UV-Vis spectroscopy is widely applied for investigating protein-ligand interaction and structural changes that might have occurred because of it [36][37][38]. e protein molecules present in the complex absorb light at λ max 280 nm, primarily due to amino acid residues Phe, Trp, and Tyr present in BSA, and the other absorption peak in BSA occurs at 205 nm and is attributed to the polypeptide backbone of BSA.…”

Study of Interactions of an Anticancer Drug Neratinib With Bovine Serum Albumin: Spectroscopic and Molecular Docking Approach

“…Plasma proteins act as carriers for transportation of drugs and other compounds. Amongst the various plasma proteins, serum albumin is the most abundant protein and it plays a vital role in transportation of drug ligands (Jahanban-Esfahlan et al, 2015 ; Wani et al, 2017b , c ). Several tyrosine kinase inhibitors have been studied for their interaction with bovine serum protein (BSA) (Shen et al, 2015 ) and in this study, the interaction of neratinib with BSA was explored.…”

Study of the Interactions of Bovine Serum Albumin with the New Anti-Inflammatory Agent 4-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-N′-[(4-ethoxy-phenyl)methylidene]benzohydrazide Using a Multi-Spectroscopic Approach and Molecular Docking

“…Serum albumin (SA) is the major protein involved in the transport of drug ligands, thus affecting the ADME (absorption, distribution, metabolism and excretion) of these drugs [ 13 , 14 , 15 ]. Thus the first step in evaluation of the pharmacokinetics of these drug ligands is to investigate its affinity towards SA [ 16 ].…”

“…BSA being the model protein due to its structural resemblance to HSA and its low-cost and obtainability was used to study the interaction between the BSA and 6P . The biophysical interaction of 6P with BSA was studied using multi-spectroscopic studies along with molecular docking [ 15 , 17 , 18 ]. The study will provide a great insight regarding the pharmacokinetic behavior of the 6P in-vivo.…”