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On the interactions between pharmacologically-relevant compounds and model membranes

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Author(s):
Priscilla Freddi
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Antônio José da Costa Filho; Eduardo Maffud Cilli; Ronny Rocha Ribeiro
Advisor: Antônio José da Costa Filho
Abstract

Sulfonamides and their different derivatives are extensively used in Medicine due to their pharmacological properties, such as antibacterial activity. Modified toxicological properties have been observed when those sulfonamides are administered in the form of metal complexes. In this work, we used the molecules sulfadimethoxine (4-p-aminobenzenesulfonamido-2,6-dimethoxypyrimidine) and sulfisoxazole (N (1) - (3,4-dimethyl-5-isoxazolyl) sulfanilamide) complexes with Cu(II) to assess their mechanism of interaction with lipid model membranes. Differential Scanning Calorimetry (DSC) and Electron Paramagnetic Resonance (EPR) experiments were carried out to monitor the influence of the complexes on the lipid thermotropic behavior. Samples consisting of the multilamellar vesicles of dipalmitoylphosphatidylcholine (DDPC) and, in the case of EPR, spin labeled phospholipids were used as models for the membrane. DSC results showed that the presence of the complexes affects both the pre-transition and the main phase transition of the lipids in the membrane. A disordering effect is evidenced by the decrease in Tm and Tp values. ESR results showed that the major alterations are detected in the lipid gel phase and for the labels positioned close to the lipid-water interface. Overall our results indicate that non-specific interactions between the complexes and the membrane might be a mechanism used by the drugs to overcome the physical barriers found in the cell. (AU)

FAPESP's process: 11/15572-4 - Interactions of metal complexes with model membranes: Electron Paramagnetic Resonance and Differential Scannning Calorimetry Studies
Grantee:Priscilla Freddi
Support Opportunities: Scholarships in Brazil - Master