Partition into dppc bilayers of dihydropyrimidine analogues with larvicidal activity.

MIGUEL V; SANCHEZ BORZONE, M; MARIANI, ME; GARCIA DA

Tucumán,

Congreso; III Latin American Federation of Biophysical Societies (LAFeBS).; 2016

Soc Arg de Biofísica

Two recently synthesized dihydropyrimidines (DHPMs) analogues have demonstrated larvicideand repellent activity against Anophelesarabiensis. DHPMs high lipophilicity suggests that thesecompounds may interact directly with the membrane and modify their biophysicalproperties. Experimental results indicate thattheir presence between lipid molecules would induce an increasingintermolecular interaction, diminishing the bilayer fluidity mainly at thepolar region (Sanchez-Borzone et al. unpublished results). Spatially resolvedfree energy profiles of DHPMs partition into a DPPC bilayer in theliquid-crystalline phase were obtained through PMF calculations using anumbrella sampling technique as a function of the distance to the center of thebilayer along its normal axis z [ΔG(z)]. In addition, we performed free diffusion MDsimulations to gain insight into the specific interactions of each compoundwith the bilayer, and analyzed the chemical groups that interact when DHPMenters the bilayer following the variation of the minimum distance among thesegroups. In agreement with the experimental assays, PMF profiles and MDsimulations showed that DHPMs are able to partition into DPPC bilayers;penetrating into the membrane and stablishing hydrogen bonds with the carbonylmoiety and interacting in less extend with phosphate groups. Although theincrease in order parameter values was mild, the presence of DHPMs moleculesinduced a more order state in hydrocarbonate chains.