Abstract

The interaction of novel chemical compounds with biological membranes is a critical area of research, particularly in the development of new therapeutics. This study investigated the molecular mechanisms of action of three dicyclohexyl-containing O-iminoisourea derivatives, specifically dicyclohexylcarbamimidoyl oximes, on model lipid membranes. The research objective was to characterize the compounds' effects on the electrical and structural properties of both uncharged (POPC) and negatively charged (POPG) lipid bilayers. Methods employed included electrophysiological measurements on planar lipid bilayers and fluorescence-based leakage assays using unilamellar vesicles, complemented by differential scanning microcalorimetry (DSC). Key findings revealed that while all tested compounds had minimal effect on uncharged membranes, one derivative, oxime **2**, significantly increased the boundary potential of negatively charged POPG membranes by 40 mV. Furthermore, oxime **2** demonstrated a superior ability to induce calcein leakage from POPG liposomes, suggesting the formation of ion-permeable pores. DSC data confirmed that the enhanced activity of oxime **2** was correlated with a greater disordering effect on the lipid bilayer structure. These results are significant for understanding the structure-activity relationship of these compounds and provide a basis for selecting matrices for further chemical modification in the development of potential anticancer drugs.