Halogenated flavonoids have shown promising biological activities due to their unique structural features. In this study, we extensively review six novel halogenated flavonoids, with different conformations and positions of chloride and bromonium atoms. Our research aimed to investigate their effects on liposome membranes. We selected two different liposome models, DPPC/chol and membrane mimicking the composition of cancer cell membranes (MM). Experimental techniques such as fluorescence-based assays, Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and molecular dynamics simulations (MD) were employed. By monitoring changes in the signal of fluorescent probes, we could gain insights into the interactions of these compounds with hydrophobic as well as hydrophilic regions of the liposome bilayer. Furthermore, we employed FTIR analysis to gain a deeper understanding of the structural changes occurring upon interaction with the lipids. In addition, we evaluated the influence of halogenated flavonoids on lipid oxidation by exposing the liposome membranes to different oxidative conditions. MD simulations provided atomistic insights into the interaction between flavonoids and model lipid bilayers. The results revealed that halogenated flavonoids preferentially interact with the polar region of the liposome membrane, and their structural variations significantly influence this interaction. The combination of experimental data and in silico analysis offers valuable tools for elucidating the molecular mechanisms underlying the bioactivity of these compounds. It can aid in developing novel therapeutic agents.
The research was cofinanced by the statutory activities of the Department of Physics and Biophysics of Wroclaw University of Environmental and Life Sciences and by the Wrocław University of Environmental and Life Sciences (Poland) as the PhD. research program number N020/0010/23 „Bon doktoranta SD UPWr”