In vivo studies of 5-arylethenylbenzofuroxans in acute murine models of Chagas' disease

被引：21

作者：

Boiani, Lucia ^{[1
]}

Davies, Carolina ^{[2
]}

Arredondo, Carolina ^{[3
]}

Porcal, Williams ^{[1
]}

Merlino, Alicia ^{[1
]}

Gerpe, Alejandra ^{[1
]}

Boiani, Mariana ^{[1
]}

Pacheco, Jose Pedro ^{[3
]}

Basombrio, Miguel Angel ^{[2
]}

Cerecetto, Hugo ^{[1
]}

Gonzalez, Mercedes ^{[1
]}

机构：

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

[2] Univ Salta, Inst Patol Expt, Salta, Argentina

[3] Univ Republica, Fac Vet, Lab Anat Patol, Montevideo, Uruguay

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 43卷 / 10期

关键词：

Chagas; Arylethenylbenzofuroxan; In vivo studies;

D O I：

10.1016/j.ejmech.2007.12.016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

5-Arylethenylbenzofuroxan derivatives with high in vitro anti-Trypanosoma cruzi activity were studied in vivo using acute murine models of Chagas' disease. The selected compounds, as pure isomeric forms, 1, 2, 3 and 4, or as equimolecular mixture of geometric isomers, 1:2, 3:4, 5:6 were studied against different T. cruzi strains. Consequently, Tulahuen 2 strain, Colombiana strain (resistant to Nifurtimox and Benznidazole), and two different wild strains, one isolated from the wild reservoir Didelphis marsupialis and another one from Uruguayan patients, were selected. No relevant signs of in vivo toxicity were observed with the benzofuroxans orally administered. Compound 1 and the mixture of isomers 1:2 were the best for treating infection against the four studied strains. (C) 2007 Elsevier Masson SAS. All rights reserved.

引用

页码：2229 / 2237

页数：9

共 26 条

[1]

Aguirre G, 2006, PHARMAZIE, V61, P54

[2] New potent 5-substituted benzofuroxans as inhibitors of Trypanosoma cruzi growth:: Quantitative structure-activity relationship studies [J].

Aguirre, G ;

Boiani, L ;

Boiani, M ;

Cerecetto, H ;

Di Maio, R ;

González, M ;

Porcal, W ;

Denicola, A ;

Piro, OE ;

Castellano, EE ;

Sant'Anna, CMR ;

Barreiro, EJ .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (23) :6336-6346

[3] Benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as potential antitrypanosomal drugs.: Part 3:: Substituents-clustering methodology in the search for new active compounds [J].

Aguirre, G ;

Boiani, L ;

Cerecetto, H ;

Di Maio, R ;

González, M ;

Porcal, W ;

Denicola, A ;

Möller, M ;

Thomson, L ;

Tórtora, V .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (23) :6324-6335

[4]

Aguirre G, 2002, ARCH PHARM, V335, P15, DOI 10.1002/1521-4184(200201)335:1&lt

[5]

15::AID-ARDP15&gt

[6]

3.0.CO

[7]

2-8

[8]

Castro J A, 1988, Biomed Environ Sci, V1, P19

[9] Synthesis and antitrypanosomal evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives.: Structure-activity relationships. [J].

Cerecetto, H ;

Di Maio, R ;

González, M ;

Risso, M ;

Sagrera, G ;

Seoane, G ;

Denicola, A ;

Peluffo, G ;

Quijano, C ;

Stoppani, AOM ;

Paulino, M ;

Olea-Azar, C ;

Basombrío, MA .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2000, 35 (03) :343-350

[10] 1,2,5-oxadiazole N-oxide derivatives and related compounds as potential antitrypanosomal drugs:: Structure-activity relationships [J].

Cerecetto, H ;

Di Maio, R ;

González, M ;

Risso, M ;

Saenz, P ;

Seoane, G ;

Denicola, A ;

Peluffo, G ;

Quijano, C ;

Olea-Azar, C .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (11) :1941-1950

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