Abstract
Bromo-Noscapine (BrNs) is a tubulin-binding cytotoxic agent with significant activity against breast and lung cancer. The mechanistic interaction insight into the binding of bovine serum albumin (BSA) with BrNs can provide critical information about the pharmacodynamics and pharmacokinetics properties. Here, various spectroscopic techniques and computational methods were employed to understand the dynamics of BrNs and BSA interaction. The intrinsic fluorescence of BSA was quenched by BrNs through a static quenching procedure. The stoichiometry of BrNs-BSA complex was 1:1 and binding constant of the complex was in the order of 103 M−1 at 298 K. Based on thermodynamic analysis, it was deduced that binding process of the BrNs with BSA was spontaneous and exothermic, and the major forces between BrNs and BSA were van der waals forces and hydrogen bonding. Moreover, results of FT-IR, CD, UV spectra concluded significant conformational change in BSA on binding with BrNs. The in vitro findings were further confirmed by in silico assays. Molecular docking showed strong interactions with score of −8.08 kcal/mol. Molecular dynamics simulation analysis also suggested the stable binding with lower deviation in RMSD and RMSF values through persistent long simulation run. This study suggests optimal efficiency of diffusion of the BrNs into the bloodstream for the treatment of cancer.
Highlights
The protein contents of body fluids are considered to be a vital index for the clinical diagnosis of any drug
Spectroscopic analyses including fluorescence, FT-IR (Fourier-transform infrared) spectroscopy, ultra violet spectrophotometry (UV) and circular dichroism (CD) analysis have been employed to explore the interaction of BrNs with bovine serum albumin (BSA) in the simulative physiological conditions
The molecular dynamics simulation studies suggested the hydrogen bond, hydrophobic and van der Waal forces are majorly responsible for drug-protein interaction and effectively prove the binding of BrNs to BSA
Summary
The protein contents of body fluids are considered to be a vital index for the clinical diagnosis of any drug. Molecular dynamics simulation studies provide the depth knowledge of interactions at the atomic level of protein and help in studying the stability of interacting complex of ligand drug with target protein and conformational changes through root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analysis. These parameters including the stability and flexibility of drug conformations are the potential factors to assess the functional and biological activity of the drug under investigation. Thereafter, molecular docking and simulation studies have been performed of BrNs with BSA
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