Interactions between pharmacologically-relevant molecules and model membranes: a molecular perspective

• Grant number: 11/17155-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2011
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Rafael Pianca Barroso
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 14/09299-1 - Interactions of antimalarials with the ion channel model MVP, BE.EP.PD

Abstract

The project has as its main goal the study of the interactions between pharmacologically-relevant molecules and model membranes from a molecular perspective. To do so we will use Electron Paramagnetic Resonance and Differential Scanning Calorimetry, besides other usual biophysical techniques that could complement our investigation. As model membranes, we will employ lipid bilayers composed by anioinic and/or zwitterionic phospholipids. The molecules under investigation will be: amodiaquine, artesunate, paromimicin, and copper compolexes with anticell activity, Amodiaquine and artesunate are commonly used in the treatment of Malaria and paromomicin in the treatement of Leishmaniases. The copper complexes, on the other hand, are derivatives of dipeptides or sulphas that prevented the growth of cell cultures, such as tumoral cells, as observed by our collaborator Prof. Maria Torre (Uruguay). We will investigate the effects of the presence of the molecules on the bilayer organization as we vary experimental parameters, such as ionic strength, drug/lipid molar ratio and membrane composition. In all cases, we are interested in a more basic aspect of the process, ie, the molecular mechanism used by the compound to effectively surpass the physical barrier represented by the model membrane, thus gaining access to the cell interior. Obviously, the exact way employed by the molecule to achieve its anti-cell activity can be rather complicated and is not the main theme under study in this project. However, the study of the non-specific interactions can certainly produce relevant information for the future design of new drugs and/or optimization of the drugs already in use.