Interaction of serum carrier protein with anticancer drugs, PCZ and PXN on binary and ternary systems through...

We explored binding mechanism and conformational alteration of anticancer drugs, PCZ and PXN with HSA in binary and ternary combinations . The binding constant value for HSA-PCZ and HSA-PXN systems obtained from fluorescence quenching experiments are 2.7417 × 10⁴ L/mol and 1.603 × 10⁴ L/mol showed that the affinity of PCZ is more than PXN towards HSA. Far-UVCD spectroscopy study of HSA in presence of PCZ/PXN individually and in combination substantiated that they destabilized the secondary structure of the protein in the order of HSA-PXN > HSA-PXN-PCZ > HSA-PCZ . To see the conformational change in HSA due to drug binding, we have also performed UV-visible, synchronous and 3D fluorescence methods. All the methods proving the same fact that both PCZ and PXN alter the microenvironment of HSA near tryptophan and tyrosine amino acid residue due to complex formation. Experimental results further validated by computational techniques like docking, simulation and DFT. Molecular docking study shows the binding sites, nature of interactions which exactly supports our fluorescence result. Energy gap between Frontier Molecular Orbitals (FMO) of HSA-PCZ/PXN complex was found to be higher than free drug molecules which indicated that the greater molecular stability of complexes were formed. Additionally, we performed MD simulation to study the structural stability of HSA both unbound and bound to PCZ/PXN. This study is expected to be of paramount importance for getting insights of their transportation in human body and could be highly beneficial in further investigating their oncogenic properties.