PARTITION INTO DPPC BILAYERS OF DIHYDROPYRIMIDINE ANALOGUES WITH LARVICIDAL ACTIVITY.

MIGUEL V; SANCHEZ-BORZONE M; MARIANI, M. E.; GARCÍA, D. A.

San Miguel de Tucumán

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

Sociedad Argentina de Biofísica

Two recently synthesized dihydropyrimidines (DHPMs) analogues havedemonstrated larvicide and repellent activity against Anopheles arabiensis. DHPMs high lipophilicity suggests that these compounds mayinteract directly with the membrane and modify their biophysical properties. Experimental results indicate that their presence between lipidmolecules would induce an increasing intermolecular interaction, diminishing the bilayer fluidity mainly at the polar region (SanchezBorzone et al. unpublished results). Spatially resolved free energy profiles of DHPMs partition into a DPPC bilayer in the liquid-crystallinephase were obtained through PMF calculations using an umbrella sampling technique as a function of the distance to the center of the bilayeralong its normal axis z [G(z)]. In addition, we performed free diffusion MD simulations to gain insight into the specific interactions ofeach compound with the bilayer, and analyzed the chemical groups thatinteract when DHPM enters the bilayer following the variation of theminimum distance among these groups. In agreement with the experimental assays, PMF profiles and MD simulations showed that DHPMsare able to partition into DPPC bilayers; penetrating into the membraneand stablishing hydrogen bonds with the carbonyl moiety and interacting in less extend with phosphate groups. Although the increase in orderparameter values was mild, the presence of DHPMs molecules induceda more order state in hydrocarbonate chains.Acknowledgements: This work was supported by grants from SECyTUNC, FONCYT-MinCyT and CONICET