Furoxan-, alkylnitrate-derivatives and related compounds as anti-trypanosomatid agents:: Mechanism of action studies

被引：37

作者：

Boiani, Lucia ^{[1
]}

Aguirre, Gabriela ^{[1
]}

Gonzalez, Mercedes ^{[1
]}

Cerecetto, Hugo ^{[1
]}

Chidichimo, Agustina ^{[2
]}

Cazzulo, Juan J. ^{[2
]}

Bertinaria, Massimo

Guglielmo, Stefano

机构：

[1] Univ Repub, Fac Ciencias, Fac Quim, Dept Quim Organ, Montevideo 11400, Uruguay

[2] Univ Nacl Gen San Martin, CONICET, Inst Invest Biotecnol, RA-1650 San Martin, Buenos Aires, Argentina

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 17期

关键词：

furoxan; Chagas disease; nitric oxide;

D O I：

10.1016/j.bmc.2008.07.077

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

A series of over a hundred furoxans, alkylnitrates and related compounds were studied as growth inhibitors of the two major kinetoplastids of Latin America, Trypanosoma cruziand Leishmania spp., in in vitro assays. The most active compounds showed 50% inhibitory doses of the same order of that of Nifurtimox and Miltefosine, reference drugs used to treat Chagas Disease and Leishmaniasis respectively. Among the studied compounds derivative 4, presenting excellent inhibitory activity against the tryposmastigote and amastigote forms of T. cruzi, has emerged as a lead compound. Mechanism of action seems to involve mitochondrial dehydrogenases as a distinct effect with respect to Nifurtimox. Excreted metabolites, studied by NMR, showed a significant decrease in succinate, confirming the observed effect on the mitochrondrial dehydrogenases. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7900 / 7907

页数：8

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