In vitro activity of scorpiand-like azamacrocycle derivatives in promastigotes and intracellular amastigotes of Leishmania infantum and Leishmania braziliensis

被引：25

作者：

Marin, Clotilde ^{[1
]}

Paz Clares, M. ^{[2
]}

Ramirez-Macias, Inmaculada ^{[1
]}

Blasco, Salvador ^{[2
]}

Olmo, Francisco ^{[1
]}

Soriano, Conxa ^{[3
]}

Verdejo, Begona ^{[2
]}

Jose Rosales, Maria ^{[1
]}

Gomez-Herrera, David ^{[1
]}

Garcia-Espana, Enrique ^{[2
]}

Sanchez-Moreno, Manuel ^{[1
]}

机构：

[1] Univ Granada, Dept Parasitol, Fac Ciencias, E-18071 Granada, Spain

[2] Univ Valencia, Inst Ciencia Mol, Dept Quim Inorgan, E-46980 Valencia, Spain

[3] Univ Valencia, Dept Quim Organ, E-46100 Valencia, Spain

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 62卷

关键词：

Leishmania infantum; Leishmania braziliensis; Synthetic aza-scorpiand; Antileishmanial activity; SOD inhibition; ENERGY-METABOLISM; DIAGNOSIS; PRODUCTS; GLUCOSE;

D O I：

10.1016/j.ejmech.2013.01.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms. All the compounds are more active and less toxic than meglumine antimoniate (Glucantime). Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania. On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible. The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage. The modifications observed by H-1 NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：466 / 477

页数：12

共 27 条

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