European Journal of Medicinal Chemistry 2010-01-01

Massive screening yields novel and selectiveTrypanosoma cruzitriosephosphate isomerase dimer-interface-irreversible inhibitors with anti-trypanosomal activity

Guzmán Álvarez, Beatriz Aguirre-López, Javier Varela, Mauricio Cabrera, Alicia Merlino, Gloria V. López, María Laura Lavaggi, Williams Porcal, Rossanna Di Maio, Mercedes González, Hugo Cerecetto, Nallely Cabrera, Ruy Pérez-Montfort, Marieta Tuena de Gómez-Puyou, Armando Gómez-Puyou, Guzmán Álvarez, Beatriz Aguirre-López, Javier Varela, Mauricio Cabrera, Alicia Merlino, Gloria V. López, María Laura Lavaggi, Williams Porcal, Rossanna Di Maio, Mercedes González, Hugo Cerecetto, Nallely Cabrera, Ruy Pérez-Montfort, Marieta Tuena de Gómez-Puyou, Armando Gómez-Puyou

Index: Eur. J. Med. Chem. 45 , 5767-72, (2010)

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Abstract

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.