CONICET | Buscador de Institutos y Recursos Humanos

https://authors.elsevier.com/a/1U7dr3IyxDhtpyTwo recently synthesized dihydropyrimidines (DHPMs) analogues have demonstrated larvicide and repellent activity against Anopheles arabiensis. Their high hydrophobicity suggests that these DHPMs activities could involve the interaction with biological membranes, modifying their biophysical properties. The purpose of the present study was to characterize the interaction of both compounds with artificial membranes. Changes on the properties of dpPC films were studied using Langmuir monolayers. The presence of DHPMs in the subphase modified the interfacial characteristics of dpPC compression isotherms, causing the expansion of the monolayer, inducing the disappearance of dpPC phase transition and reducing the elasticity in the condensed phases. Moreover, both compounds showed ability to penetrate into the lipid monolayers at molecular pressures comparable to those in biological membranes. The effects of both DHPMs on the molecular organization of dpPC liposomes were measured by fluorescence anisotropy. The results indicate that their presence between lipid molecules would induce an increasing intermolecular interaction, diminishing the bilayer fluidity mainly at the polar region. Finally, we obtained spatially resolved free energy profiles of DHPMs partition into a dpPC bilayer through Potential of Mean Force calculations. In agreement with the experimental assays, these profiles showed that DHPMs are able to partition into dpPC bilayers, penetrating into the membrane at the upper carbonyl region, but are incapable of crossing the bilayer. Our results suggest that DHPMs bioactivity could involve their interaction with the lipid molecules that modulate the supramolecular organization of the biological membranes and consequently the membrane proteins functionality

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