Partition DPPC bilayers of dihydropyrimidine analogues with larvicidal activity

MIGUEL VIRGINIA; MARIELA SÁNCHEZ; MARIANI, ELISA; DANIEL GARCÍA

San Miguel de Tucumán

Congreso; III Latin American Federation of Biophysical Societies (LAFeBS) ,IX IberoAmerican Congress of Biophysics, XLV Reunion Anual SAB; 2016

Two recently synthesized dihydropyrimidines (DHPMs) analogues have demonstrated larvicide and repellent activity against Anopheles arabiensis.. DHPMs high lipophilicity suggests that these compounds may interact directly with the membrane and modify their biophysical properties. Experimental results indicate that their presence between lipid molecules would induce an increasing intermolecular interaction, diminishing the bilayer fluidity mainly at the polar region. Spatially resolved free energy profiles of DHPMs partition into a DPPC bilayer in the liquid-crystalline phase were obtained through PMF calculations using an umbrella sampling technique as a function of the distance to the center of the bilayer along its normal axis z [ΔG(z)]. Also, we performed free diffusion MD simulations to gain insight into the specific interactions of each compound with the bilayer. We analyzed the chemical groups that interact when DHPM enters the bilayer following the variation of the minimum distance among these groups. In agreement with the experimental assays, PMF profiles and MD simulations showed that DHPMs are able to partition into DPPC bilayers, penetrating into the membrane and stablishing hydrogen bonds with the carbonyl moiety and interact in less extend with phosphate groups. Although the increase in SCD values was mild, the presence of DHPMs molecules induced a more order state in hydrocarbonate chains.