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

Abstract

Binding of therapeutic agents to plasma proteins, particularly to serum albumin, provides valuable information in the drug development. This study was designed to evaluate the binding interaction of neratinib with bovine serum albumin (BSA). Neratinib blocks HER2 signaling and is effective in trastuzumab-resistant breast cancer treatment. Spectrofluorometric, UV spectrophotometric, and fourier transform infrared (FT-IR) and molecular docking experiments were performed to study this interaction. The fluorescence of BSA is attributed to the presence of tryptophan (Trp) residues. The fluorescence of BSA in presence of neratinib was studied using the excitation wavelength of 280 nm and the emission was measured at 300-500 nm at three different temperatures. Neratinib quenched the BSA intrinsic fluorescence by static mechanism. A complex formation occurred due to the interaction leading to BSA absorption shift. The fluorescence, UV- absorption, three dimensional fluorescence and FT-IR data showed conformational changes occurred in BSA after interaction with neratinib. The binding constant values decreased as the temperature increased suggesting an instable complex formation at high temperature. Site I (sub-domain IIA) was observed as the principal binding site for neratinib. Hydrogen bonding and Van der Waals forces were suggested to be involved in the BSA-neratinib interaction due to the negative values of entropy and enthalpy changes.

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

“…e scoring function 1 was put to London dG, and the function 2 was put to GBVI/WSA dG. e most appropriate interaction was designated as per the root mean square values obtained [21].…”

“…e 3D fluorescence spectroscopy has gained quite popularity to access the protein structural changes. It gives a detailed account of the conformation modifications in protein due to protein-ligand interaction [21,43].…”

“…us, the binding mechanism of drug with albumin, and its distribution needs to be investigated [20][21][22][23].…”

Entropy‐driven binding of octyl gallate in albumin: Failure in the application of temperature effect to distinguish dynamic and static fluorescence quenching

“…In this regard, bovine serum albumin (BSA) has been applied in numerous studies involving different ligands; and fluorescence quenching is the usual physicochemical approach to study these interactions . BSA is used as a model protein to study the interaction between drugs and albumins . Indeed, due to the physiological role of serum albumin as the main drug carrier, these studies are fundamental in the elucidation of pharmacokinetic properties of developing drugs …”

Biological evaluation of a novel amino acid‐based macrocyclic Mn(III) and Fe(III) complexes

“…Since the Stern‐Volmer quenching constants K sv is found to decrease with increase in temperature and the K q values were found to be larger than 2.0 x 10 10 Lmol −1 s −1 reported for the maximum diffusion quenching rate constant of various quenchers with biopolymers, the quenching of BSA by the metal complexes could be static and not dynamic quenching.…”