Colloids Surf B Biointerfaces 2026 Jun 24;267:115924. doi: 10.1016/j.colsurfb.2026.115924.

Cooperative effects of natural acetylenic acetogenins fromPorcelia macrocarpaon lipid packing and mechanical stability of Langmuir monolayers as protozoan membrane models.

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This study investigates the synergistic interfacial behavior of two natural bioactive acetylenic acetogenins, (2S,3R,4R)-3 hydroxy-4-methyl-2-(n-eicos-11'-yn-19'-enyl)butanolide (1) and (2S,3R,4R)-3-hydroxy-4 methyl-2-(n-eicos-11'-ynyl)butanolide (2), obtained from Brazilian plant Porcelia macrocarpa (Annonaceae) and their interactions with membrane models using Langmuir films. Previous biological studies demonstrated that mixtures of 1 and 2 exhibit enhanced antiparasitic activity compared to the isolated compounds, although the physicochemical basis for this synergism remained unclear. In the present study, equimolar mixtures of 1 and 2 were investigated through surface pressure-area (π-A) isotherms, surface compressional modulus, Brewster Angle Microscopy (BAM), and rheological analyses, both as pure films and incorporated into dipalmitoylphosphatidylethanolamine (DPPE) monolayers, used as protozoan membrane models. The mixture of 1 and 2 monolayer exhibited distinct interfacial organization compared to the pure compounds, including suppression of phase-transition regions characteristic of 2, delayed onset of pre-collapse instabilities, and enhanced condensation before collapse. BAM images revealed cooperative effects between the compounds, leading to more homogeneous monolayers prior to instability and more interconnected collapse structures after compression. When incorporated into DPPE monolayers, the mixture of 1 and 2 induced expansion, phase separation, and mechanical instabilities at biologically relevant surface, indicating substantial perturbation of membrane packing. The combined results demonstrate that the interplay between the different unsaturation patterns of the studied acetogenins modulates molecular organization, phase behavior, and membrane-disruptive properties at interfaces. These findings provide physicochemical insights into the synergistic bioactivity previously observed for acetogenin mixtures and highlight the importance of collective intermolecular interactions in the membrane activity of natural products.

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