Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine

Breidbach, Tanja; Scory, Stefan; Krauth‐Siegel, R. Luise; Steverding, Dietmar

doi:10.1016/s0020-7519(01)00310-1

Cited by 51 publications

(46 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 mM (Breidbach et al 2002 ;Merschjohann and Steverding, 2006). These chelators act by iron sequestration, preventing the incorporation of iron into newly synthesized enzymes, rather than stripping iron from already active proteins.…”

Section: R O N M E T a B O L I S M A S A D R U G T A R G E Tmentioning

confidence: 99%

Iron metabolism in trypanosomatids, and its crucial role in infection

Taylor

Kelly

2010

Parasitology

View full text Add to dashboard Cite

Iron is almost ubiquitous in living organisms due to the utility of its redox chemistry. It is also dangerous as it can catalyse the formation of reactive free radicals -a classical double-edged sword. In this review, we examine the uptake and usage of iron by trypanosomatids and discuss how modulation of host iron metabolism plays an important role in the protective response. Trypanosomatids require iron for crucial processes including DNA replication, antioxidant defence, mitochondrial respiration, synthesis of the modified base J and, in African trypanosomes, the alternative oxidase. The source of iron varies between species. Bloodstream-form African trypanosomes acquire iron from their host by uptake of transferrin, and Leishmania amazonensis expresses a ZIP family cation transporter in the plasma membrane. In other trypanosomatids, iron uptake has been poorly characterized. Iron-withholding responses by the host can be a major determinant of disease outcome. Their role in trypanosomatid infections is becoming apparent. For example, the cytosolic sequestration properties of NRAMP1, confer resistance against leishmaniasis. Conversely, cytoplasmic sequestration of iron may be favourable rather than detrimental to Trypanosoma cruzi. The central role of iron in both parasite metabolism and the host response is attracting interest as a possible point of therapeutic intervention.

show abstract

Section: R O N M E T a B O L I S M A S A D R U G T A R G E Tmentioning

confidence: 99%

Iron metabolism in trypanosomatids, and its crucial role in infection

Taylor

Kelly

2010

Parasitology

View full text Add to dashboard Cite

show abstract

“…Compound 5 was much less active on both strains. Although the rule-of-five established by Lipinski [24,25] invites exceptions (e.g., erythromycin), the high molecular weight (MW 688) and the high lipophilicity of 5 render it less drug-like [26] which should perturb its transport to the food vacuole of the parasite. The presence of two bulky ferrocenyl moieties in compound 5 could also destabilize the interaction (steric hindrance) of the quinoline cycle with ferriprotoporphyrin IX leading to a weaker antiparasitic activity than for compound 4.…”

Section: Resultsmentioning

confidence: 99%

Easily synthesized antimalarial ferrocene triazacyclononane quinoline conjugates

Biot

Dessolin

Ricard

et al. 2004

Journal of Organometallic Chemistry

View full text Add to dashboard Cite

“…Previous studies have revealed that growth of cells even those of trypanosomes can be successfully inhibited by depriving the cells of iron 27 . Consequently, iron-chelation has thus been adopted as an attractive and possible strategy for new anti-parasite drugs and treatment of sleeping sickness 11,28 . Ribonucleotide reductase is a cell cycle induced enzyme 12 that is equally dependent on continuous availability of recyclable iron 2 .…”

Section: Discussionmentioning

confidence: 99%

Iron chelation excludes protein synthesis inhibition in the tetracycline management of African trypanosomosis

et al. 2005

View full text Add to dashboard Cite

Ribonucleotide reductase, an iron requiring enzyme necessary in the production of deoxyribonucleotides required for replication in cell division and proliferation is induced during the S phase of the cell cycle. We have compared the trypanocidal properties of four antibiotics that show bactericidal activities by destabilizing ribosome-mRNA complex to inhibit protein synthesis. Tetracycline and oxytetracycline that have iron chelating properties extended the lifespan of trypanosome infected rats from 6 and 5 days of control to 15 and 12 days respectively while chloramphenicol and streptomycin that have no iron chelating properties could not extend the lifespan of infected rats. We confirm our earlier report that iron chelation plays a prominent role in the tetracycline management of African trypanosomosis.

show abstract

Growth inhibition of bloodstream forms of Trypanosoma brucei by the iron chelator deferoxamine

Cited by 51 publications

References 30 publications

Iron metabolism in trypanosomatids, and its crucial role in infection

Iron metabolism in trypanosomatids, and its crucial role in infection

Easily synthesized antimalarial ferrocene triazacyclononane quinoline conjugates

Iron chelation excludes protein synthesis inhibition in the tetracycline management of African trypanosomosis

Contact Info

Product

Resources

About