Identification of Novel Chemical Scaffolds Inhibiting Trypanothione Synthetase from Pathogenic Trypanosomatids

DIEGO BENÍTEZ; ANDREA MEDEIROS; LUCÍA FIESTAS; ESTEBAN A. PANOZZO-ZENERE; FRANZISCA MAIWALD; THEODORA CALOGEROPOULOU; ANASTASIA DETSI; MARINA ROUSSAKI; KYRIAKOS C. PROUSIS; TIMO JAEGER; JONAS ARLAUSKAS; LUCÍJA PETERLIN MAIč; CONRAD KUNICK; GUILLERMO R. LABADIE; LEOPOLD FLOHÉ; MARCELO A. COMINI

PLOS NEGLECTED TROPICAL DISEASES

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016 vol. 10

1935-2735

The search for novel chemical entities targeting essential and parasite-specific pathways is considered a priority for neglected diseases such as trypanosomiasis and leishmaniasis. The thiol-dependent redox metabolism of trypanosomatids relies on bis-glutathionylspermidine [trypanothione, T(SH2)], a low molecular mass cosubstrate absent in the host. In pathogenic trypanosomatids, a single enzyme, trypanothione synthetase (TryS), catalyzes trypanothione biosynthesis, which is indispensable for parasite survival. Thus, TryS qualifies as an attractive drug target candidate.