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

•Detailed informations on the serum albumin binding properties of cytotoxic cyclic C5-curcuminoid derivatives with different biological activity.•UV–Vis studies and fluorescence methods were used.•The binding sites were determined and the binding constants and the corresponding thermodynamic parameters of the interaction were calculated.•The spectroscopic results are supported by in silico studies as well. 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. [Display omitted]