Mode of Action on Trypanosoma and Leishmania spp.
In this chapter, the most common molecular targets and mechanisms of action of anti-trypanosomatid drugs are described: biosynthesis of sterols, trypanothione pathway, purine salvage pathway, cysteine proteinases, trans-sialidase, metallocarboxypeptidases, tubulin, calcium homeostasis and pyrophosphate metabolism, heme uptake and degradation, glycolytic pathway, DNA interaction, oxidative stress and apoptosis. Interaction of the sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of enzymes as cruzipain and trypanothione reductase, the apoptosis induction and the ability of this type of compounds to inhibit sterol biosynthesis will be also discussed.
KeywordsAnti-trypanosomatid drugs Drug targets Sterol biosynthesis Trypanothione pathway Proteinases Trans-sialidase Tubulin Heme Oxidative stress Apoptosis
- Fernandes Rodrigues JC, Concepcion JL, Rodrigues C et al (2008) In vitro activities of ER-119884 and E5700, two potent squalene synthase inhibitors, against Leishmania amazonensis: antiproliferative, biochemical, and ultrastructural effects. Antimicrob Agents Chemother 52:4098–4114CrossRefPubMedPubMedCentralGoogle Scholar
- Scory S, Stierhof YD, Caffrey CR et al (2007) The cysteine proteinase inhibitor Z-Phe-Ala-CHN2 alters cell morphology and cell division activity of Trypanosoma brucei bloodstream forms in vivo. Kinetoplastid Biol Dis 6:2. https://doi.org/10.1186/1475-9292-6-2 CrossRefPubMedPubMedCentralGoogle Scholar
- Silva-Jardim I, Thiemann OH, Anibal F de F (2014) Leishmaniasis and Chagas disease chemotherapy: a critical review. J Braz Chem Soc 25:1810–1823Google Scholar