Selective Modulation of Lipid Langmuir Monolayers by Methyl Dehydrodieugenol: Insights into Its Interaction with Compressibility-Modulating Lipid Interfaces for Antiprotozoal Applications.

This study investigates the interaction of methyl dehydrodieugenol (MDHDE) with model lipid monolayers to elucidate its potential as a membrane-targeting therapeutic agent. Langmuir monolayer experiments were conducted using dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE), and cholesterol to mimic the compressible and condensed states of protozoal and mammalian membranes. Surface pressure-area isotherms revealed that MDHDE reduced the molecular packing density of the lipids at biologically relevant surface pressures, suggesting attractive interactions at the molecular level. While the surface compressional modulus decreased for all monolayers, the dilatational elasticity measurements indicated an increase in the elastic character of the DOPC monolayer upon MDHDE incorporation. Surface potential measurements indicated distinct effects on electrostatic properties, with MDHDE causing a sustained decrease in potential for DOPC and convergence of values at collapse for DOPE. Brewster angle microscopy showed increased domain density in DOPC and coalescence of domains in DOPE upon MDHDE incorporation, whereas cholesterol monolayers were unaffected. Polarization-modulation infrared reflection-absorption spectra confirmed MDHDE-induced changes in lipid surface arrangement and hydration in both hydrophobic and hydrophilic regions of the monolayers, demonstrating selective interactions based on lipid composition. These findings highlight the MDHDE's ability to modulate membrane properties in a lipid-dependent manner, underscore the importance of lipid selectivity in designing membrane-active compounds, and provide a foundation for the further development of MDHDE as an antiprotozoal agent.