Publication

Abstract : The interaction between halogenated thiophene chalcones and the main plasma protein, i.e. human serum albumin (HSA), has been investigated in vitro under simulated physiological condition by spectroscopic techniques (UV–Vis, fluorescence and circular dichroism), zeta potential and molecular docking. Fluorescence quenching of albumin by the thiophene chalcones T1–T9 (kq≈1012M−1s−1) indicates a static quenching mechanism; however, for the samples T02 and T5 the possibility of a combination of simultaneous static and dynamic quenching mechanism was detected. According to FRET theory, the energy transfer from HSA to the thiophene chalcones occurs with high probability. Modified Stern-Volmer binding constants (Ka≈104M−1), circular dichroism and potential surface data suggest that the association HSA:thiophene chalcone is moderate and there is not a significant perturbation on the secondary structure of albumin, as well as on its surface. Thermodynamic parameters indicate a spontaneous (ΔG°<0) and a probably entropy-driven (ΔS°<0) association, typical of hydrophobic interactions. On the other hand, for T5 besides the entropy-driven association there is also a contribution from the enthalpy change (ΔH°<0). Molecular docking results suggest hydrogen bonding and hydrophobic interactions as the main binding forces in the association between HSA and all thiophene chalcones; however, molecular docking calculations for T05 detected a high possibility of an electrostatic interaction between the fluorine atom and the Lys-194 residue.