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T. brucei whole cell proteome changes upon exposure to the 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 liquid chromatography coupled with tandem mass spectrometry (LC-MSMS) to quantify the effects of PH-39 exposure on the global protein landscape in T. brucei.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Trypanosoma Brucei

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Trypanosomiasis

SUBMITTER: Martin Zoltner

LAB HEAD: Martin Zoltner

PROVIDER: PXD043204 | Pride | 2024-03-12

REPOSITORIES: Pride

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			Action	DRS
	1097-ph1.raw	Raw
	1097-ph2.raw	Raw
	1097-ph3.raw	Raw
	1097-tc1.raw	Raw
	1097-tc2.raw	Raw

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