Examination of the mode of action of the almiramide family of natural products against the kinetoplastid parasite Trypanosoma brucei.

ABSTRACT: Almiramide C is a marine natural product with low micromolar activity against Leishmania donovani, the causative agent of leishmaniasis. We have now shown that almiramide C is also active against the related parasite Trypanosoma brucei, the causative agent of human African trypanosomiasis. A series of activity-based probes have been synthesized to explore both the molecular target of this compound series in T. brucei lysates and site localization through epifluorescence microscopy. These target identification studies indicate that the almiramides likely perturb glycosomal function through disruption of membrane assembly machinery. Glycosomes, which are organelles specific to kinetoplastid parasites, house the first seven steps of glycolysis and have been shown to be essential for parasite

SUBMITTER: Sanchez LM 

PROVIDER: S-EPMC3971013 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature