Effects of the antimalarial drug primaquine on the dynamic structure of lipid model membranes

Autor(es)

Basso, Luis G. M. ^[1] ; Rodrigues, Renata Z. ^[2] ; Naal, Rose M. Z. G. ^{[2, 3]} ; Costa-Filho, Antonio J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, Grp Biofis Mol Sergio Mascarenhas, Dept Fis & Informat, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Quim & Fis, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Inst Natl Ciencia & Tecnol Bioanalit, BR-13083970 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1808, n. 1, p. 55-64, JAN 2011.
• Citações Web of Science: 24

Resumo

Primaquine (PQ) is a potent therapeutic agent used in the treatment of malaria and its mechanism of action still lacks a more detailed understanding at a molecular level. In this context, we used differential scanning calorimetry (DSC), pressure perturbation calorimetry (PPC), and electron spin resonance (ESR) to investigate the effects of PQ on the lipid phase transition, acyl chain dynamics, and on volumetric properties of lipid model membranes. DSC thermograms revealed that PQ stabilizes the fluid phase of the lipid model membranes and interacts mainly with the lipid headgroups. This result was revealed by the great effect on the pretransition of phosphatidylcholines and the destabilization of the inverted hexagonal phase of a phosphatidylethanolamine bilayer. Spin probes located at different positions along the lipid chain were used to monitor different membrane regions. ESR results indicated that PQ is effective in changing the acyl chain ordering and dynamics of the whole chain of dimyristoylphosphatidylcholine (DMPC) phospholipid in the rippled gel phase. The combined ESR and PPC results revealed that the slight DMPC volume changes at the main phase transition induced by the presence of PQ is probably due to a less dense lipid gel phase. At physiological pH, the cationic amphiphilic PQ strongly interacts with the lipid headgroup region of the bilayers. causing considerable disorganization in the hydrophobic core. These results shed light on the molecular mechanism of primaquine-lipid interaction, which may be useful in the understanding of the complex mechanism of action and/or the adverse effects of this antimalarial drug. (C) 2010 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 06/58479-6 - Interacoes de farmacos anti-malaria com modelos de membrana.
• Beneficiário: Luís Guilherme Mansor Basso
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 02/13090-3 - Estrutura dinamica de membranas lipidicas de interesse biologico: a fase hexagonal invertida e a interacao lipidio-peptideo por ressonancia paramagnetica eletronica.
• Beneficiário: Antonio José da Costa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 08/57910-0 - Instituto Nacional de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosas - INBEQMeDI
• Beneficiário: Richard Charles Garratt
• Modalidade de apoio: Auxílio à Pesquisa - Temático