Serum albumin binding studies on antiproliferative cyclic C5-curcuminoid derivatives using spectroscopic methods and molecular modelling

Cyclic C5-curcuminoid derivatives are synthetic analogues of the natural product curcumin possessing diverse pharmacological potential. We described earlier that some of the cyclic C5-curcuminoids display excellent cytotoxic activity against human neuroblastoma (SH-SY5Y) and human grade IV astrocytoma (CCF-STTG1) cell lines in low nanomolar concentrations. Some of the tested cyclic C5-curcuminoids have also proved to be able to penetrate the blood-brain barrier (BBB) model. We discovered at the same time certain structure related differences in cytotoxicity and BBB penetration rates of the compounds tested. We assumed that the differences can be due to various physicochemical behaviours toward human serum albumin (HSA) of the compounds (Huber et al., 2022). In this work, therefore, we set out to gain deeper insight into the binding nature of three selected synthetic cyclic C5-curcuminoid derivatives to human serum albumin (HSA) at different temperatures by UV-Vis absorption spectroscopy, fluorescence methods, and 3D molecular modeling simulation. The experimental results showed that the observed fluorescence quenching of HSA by the compounds is due to a complex formation of a dominantly static quenching process with a quenching constant in the order of 104-105 M-1. The binding constants, binding sites and the corresponding thermodynamic parameters of the interaction were calculated. The data suggest that conformational changes have taken place by the interaction of curcuminoids and HSA. This interaction is mainly due to hydrophobic forces.

Automated summary

In this study, the binding nature of three selected synthetic cyclic C5-curcuminoid derivatives to human serum albumin (HSA) at different temperatures was investigated using UV-Vis absorption spectroscopy, fluorescence methods, and 3D molecular modeling simulation. The experimental results revealed that the compounds formed complexes with HSA, leading to fluorescence quenching through a predominantly static quenching process with a quenching constant in the range of 104-105 M-1. The binding constants, binding sites, and thermodynamic parameters were calculated, suggesting that hydrophobic forces played a major role in the interaction between curcuminoids and HSA.