Bioctive Molecules in Phospholipid Monolayers

M.F. MARTINI; E. A. DISALVO; M PICKHOLZ

Ouro preto

Simposio; XVI Simposio Brasileiro de Química Teórica; 2011

SBQT

The elucidation at molecular level of the interactions of bioactive species with phospholipid constituents of biological membranes are of fundamental importance for the description of their mechanisms of action. Among bioactive species, those containing nitrogen atoms are of particular importance due to its direct function or as constituents of nucleic acids. Picolinamide (2-pyridinecarboxamide, PA) and nicotinamide (3-pyridinecarboxamide, NA), shown in Figure 1, are two well known bioactive isomers of pyridine-carboxamide which were found to take part in many important biological processes. In this work, we study the interaction of NA and PA with lipid monolayers, through Molecular Dynamics simulations. This kind of interactions strongly depends on the lipid head. In this way we take into account two phospholipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE). In order to recreate experimental conditions given in Ref. 1 we simulate a high guest molecule:lipid concentration (poner?). Our results for the DMPC monolayers show that both NA and PA molecules are essentially found at the lipid/water interface and strongly interact with the polar lipid water. Not significant differences were found between these bioactive species with DMPC monolayers, in good agreement with experimental results. By the other hand, dipole potential experiments had shown significant differences between the interaction of NA and PA with 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) monolayers. Simulations of these systems are in progress. Besides preliminar results shows that the DMPE monolayers are more affected by the PA than the NA bioactive molecules.