Genome-scale RNA interference profiling of Trypanosoma brucei sensitivity determinants for experimental phthalimide-based trypanocidal drug PHT-39

ABSTRACT: In a phenotypic screening approach of novel molecules composed of a synergistic combination of phthalimide, benzimidazole, and triazole scaffolds we discovered compounds with potent anti-leishmanial activity. The resulting early-lead compound PHT-39, which contains a trifluoromethyl substitution, demonstrated the highest efficacy in a Leishmania infantum intramacrophage assay, with an EC50 of 1.2+/- 3.2 μM.Cytotoxicity testing of PHT-39 in Hep-G2 cells indicated high selectivity of over 90-fold. To investigate the mechanism of action we carried out experiments in Trypanosoma brucei, which is also sensitive to PHT-39. Here we used a genome-wide RNAi library approach (PMID: 22278056; PMID: 21363968) to detect sensitivity determinants. This high-throughput phenotyping approach identified sens

INSTRUMENT(S): DNBSEQ-T7

ORGANISM(S): Trypanosoma brucei TREU927

SUBMITTER: Martin Zoltner 

PROVIDER: E-MTAB-13844 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress