Massive screening yields novel and selective Trypanosoma cruzi triosephosphate isomerase dimer-interface-irreversible inhibitors with anti-trypanosomal activity

被引：43

作者：

Alvarez, Guzman ^{[1
]}

Aguirre-Lopez, Beatriz ^{[2
]}

Varela, Javier ^{[1
]}

Cabrera, Mauricio ^{[1
]}

Merlino, Alicia ^{[1
]}

Lopez, Gloria V. ^{[1
]}

Laura Lavaggi, Maria ^{[1
]}

Porcal, Williams ^{[1
]}

Di Maio, Rossanna ^{[1
]}

Gonzalez, Mercedes ^{[1
]}

Cerecetto, Hugo ^{[1
]}

Cabrera, Nallely ^{[2
]}

Perez-Montfort, Ruy ^{[2
]}

Tuena de Gomez-Puyou, Marieta ^{[2
]}

Gomez-Puyou, Armando ^{[2
]}

机构：

[1] Univ Republica, Grp Quim Med, Lab Quim Organ, Fac Quim,Fac Ciencias, Montevideo 11400, Uruguay

[2] Univ Nacl Autonoma Mexico, Dept Bioquim & Biol Estruct, Inst Fisiol Celular, Mexico City 04510, DF, Mexico

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 12期

关键词：

T; cruzi; TIM; Massive screening; Drug discovery; CRYSTAL-STRUCTURE; PARASITE; STRAINS; AGENTS;

D O I：

10.1016/j.ejmech.2010.09.034

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：

Triosephosphate isomerase from Trypanosoma cruzi (TcTIM), an enzyme in the glycolytic pathway that exhibits high catalytic rates of glyceraldehyde-3-phosphate- and dihydroxyacetone-phosphate-isomerization only in its dimeric form, was screened against an in-house chemical library containing nearly 230 compounds belonging to different chemotypes. After secondary screening, twenty-six compounds from eight different chemotypes were identified as screening positives. Four compounds displayed selectivity for TcTIM over TIM from Homo sapiens and, concomitantly, in vitro activity against T cruzi. (C) 2010 Elsevier Masson SAS. All rights reserved.

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收藏

页码：5767 / 5772

页数：6

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