Interactions of the antimalarial amodiaquine with lipid model membranes

Autor(es)

Barroso, Rafael P. ^[1] ; Basso, Luis G. M. ^[1] ; Costa-Filho, Antonio J. ^[1]

Afiliação do(s) autor(es)

^[1] Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, Lab Biofis Mol, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Chemistry and Physics of Lipids; v. 186, p. 68-78, FEB 2015.
• Citações Web of Science: 5

Resumo

A detailed molecular description of the mechanism of action of the antimalarial drug amodiaquine (AQ) is still an open issue. To gain further insights on that, we studied the interactions of AQ with lipid model membranes composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS) by spin labeling electron spin resonance (ESR) and differential scanning calorimetry (DSC). Both techniques indicate a coexistence of an ordered DPPS-rich domain with a disordered DPPC-rich domain in the binary DPPC/DPPS system. We found that AQ slightly lowered the melting transition temperatures associated to both domains and significantly increased the enthalpy change of the whole DPPC/DPPS phase transition. DSC and ESR data also suggest that AQ increases the number of DPPC molecules in the DPPC-rich domains. AQ also causes opposing ordering effects on different regions of the bilayer: while the drug increases the ordering of the lipid acyl chains from carbon 7 to 16, it decreases the order parameter of the lipid head group and of carbon 5. The gel phase was mostly affected by the presence of AQ suggesting that AQ is able to influence more organized lipid domains. Moreover, the effects of AQand cholesterol on lipid acyl chain ordering and mobility were compared at physiological temperature and, in a general way, they are similar. Our results suggest that the quinoline ring of AQ is located completely inside the lipid bilayers with its phenol ring and the tertiary amine directed towards the head group region. The nonspecific interaction between AQand DPPC/DPPS bilayers is a combination of electrostatic and hydrophobic interactions. (C) 2014 Elsevier Ireland Ltd. All rights reserved. (AU)

• Processo FAPESP: 10/17662-8 - Ressonância magnética eletrônica em estudos de estrutura, função e interações de moléculas com interesse biológico
• Beneficiário: Antonio José da Costa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/20367-3 - Estudos estruturais e funcionais da proteína de organização e compactação do Golgi (GRASP) de Cryptococcus neoformans
• Beneficiário: Antonio José da Costa Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular