Second generation of 2H-benzimidazole 1,3-dioxide derivatives as anti-trypanosomatid agents: Synthesis, biological evaluation, and mode of action studies

被引：33

作者：

Boiani, Mariana ^{[1
]}

Boiani, Lucia ^{[1
]}

Merlino, Alicia ^{[1
]}

Hernandez, Paola ^{[1
]}

Chidichimo, Agustina ^{[2
]}

Cazzulo, Juan J. ^{[2
]}

Cerecetto, Hugo ^{[1
]}

Gonzalez, Mercedes ^{[1
]}

机构：

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

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

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 11期

关键词：

2H-Benzimidazole 1,3-dioxide; Chagas disease; Leishmaniasis; Mitochondrial dehydrogenases; N-OXIDE DERIVATIVES; POTENTIAL ANTITRYPANOSOMAL DRUGS; VISCERAL LEISHMANIASIS; CRUZI GROWTH; IN-VITRO; INHIBITORS; METABOLISM; COMPONENTS; IMIDAZOLE; MECHANISM;

D O I：

10.1016/j.ejmech.2009.06.014

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Exploring the influence of different substitution patterns of 2H-benzimidazole 1,3-dioxide derivatives (BzNO) we prepared fifteen new derivatives. Initially the BzNO were tested against Trypanosoma cruzi Tulahuen 2 strain epimastigote form rendering very potent anti-T. cruzi agents. Moreover, the BzNO were able to inhibit the growth of virulent and resistant to Benznidazole strains (CL Brener clone, Colombiana, and Y strains) and to Leishmania braziliensis. Interestingly, BzNO exhibited very high selectivity index and particularly the spiro-BzNO 13 provokes an important diminution of amastigotes in Vero cells. Besides, it was found a diminution of acetate and glycine as excreted metabolites but without increase of parasite glucose uptake indicating that the glycosome is probably not involucrate in the 2H-benzimidazole 1,3-dioxides mechanism of action. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：4426 / 4433

页数：8

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