Effects of novel triple-stage antimalarial ionic liquids on lipid membrane models

被引：19

作者：

Ferraz, Ricardo ^{[1
,2
]}

Pinheiro, Marina ^{[3
]}

Gomes, Ana ^{[1
,2
]}

Teixeira, Catia ^{[1
,2
]}

Prudencio, Cristina ^{[2
,4
]}

Reis, Salette ^{[3
]}

Gomes, Paula ^{[1
]}

机构：

[1] Univ Porto, Dept Quim & Bioquim, LAQV REQUIMTE, Fac Ciencias, Rua Campo Alegre 687, P-4069007 Oporto, Portugal

[2] Politecn Porto, ESS, Rua Dr Antonio Bernardino de Almeida 400, P-4200072 Oporto, Portugal

[3] Univ Porto, Dept Ciencias Quim, LAQV REQUIMTE, Fac Farm, Rua Jorge Viterbo Ferreira 228, P-4050313 Oporto, Portugal

[4] Univ Porto, I3S, Rua Alfredo Allen 208, P-4200135 Oporto, Portugal

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 17期

关键词：

Ionic liquids; Liposomes; Malaria; Primaquine; Red Blood Cells; PARASITE PLASMODIUM-FALCIPARUM; ERYTHROCYTE PERMEABILITY; PRIMAQUINE; MALARIA; DERIVATIVES; LIPOSOMES; PEPTIDE; ANALOGS; CONFORMATION; AMPICILLIN;

D O I：

10.1016/j.bmcl.2017.07.006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Primaquine-based ionic liquids, obtained by acid-base reaction between parent primaquine and cinnamic acids, were recently found as triple-stage antimalarial hits. These ionic compounds displayed significant activity against both liver- and blood-stage Plasmodium parasites, as well as against stage V P. falciparum parasites. Remarkably, blood-stage activity of the ionic liquids against both chloroquine-sensitive (3D7) and resistant (Dd2) P. falciparum strains was clearly superior to those of the respective covalent (amide) analogues and of parent primaquine. Having hypothesized that such behaviour might be ascribed to an enhanced ability of the ionic compounds to permeate into Plasmodium-infected erythrocytes, we have carried out a differential scanning calorimetry-based study of the interactions between the ionic liquids and membrane models. Results provide evidence, at the molecular level, that the primaquine-derived ionic liquids may contribute to an increased permeation of the parent drug into malaria-infected erythrocytes, which has relevant implications towards novel antimalarial approaches based on ionic liquids. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：4190 / 4193

页数：4

共 37 条

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