Iron chelators as drugs against malaria pose a potential risk

Golenser, Jacob; Domb, Abraham J.; Leshem, B.; Kremsner, Peter G.; Luty, Adrian J. F.

doi:10.1179/135100003225002880

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…[ 1437 , 1489 , 1676 , 1760 - 1767 ]). Many problems remain, such as bioavailability, mis-dosing [ 1768 ] (too little iron as well as too much of it can be bad), toxicity, selectivity and so on, and their design is consequently highly non-trivial [ 1665 , 1670 ]. Nevertheless, iron chelators have demonstrated therapeutic benefits in Alzheimer's [ 1674 , 1710 , 1769 - 1771 ], Parkinson's [ 1037 , 1729 , 1772 ], cold-induced brain injury [ 1773 , 1774 ], coronary disease [ 714 , 797 ], renal diseases [ 1775 ], various kinds of infection [ 1763 ] and of course in iron overload diseases [ 1762 , 1767 ].…”

Section: Utility Of Iron Chelators In Disease Ameliorationmentioning

confidence: 99%

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

2009

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Background: The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular 'reactive oxygen species' (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation.

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Section: Utility Of Iron Chelators In Disease Ameliorationmentioning

confidence: 99%

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

2009

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“…The present study suggested that iron depletion may be an effective against Leishmania infection. However, usage of iron chelators as a possible antileishmanial therapy must be taken with great care since they could create potential health disorders for host as has been noted with other infectious agents (Golenser et al, 2003) In conclusion, the tested drug has shown to possess a promising antileishmanial activity in vitro system. Furthermore, their effect in vivo in experimental animals should be performed to draw a meaningful conclusion.…”

Section: Discussionmentioning

confidence: 95%

In vitro evaluation of the efficacy of deferoxamine against Leishmania major life cycle stages

Dajem

2010

Journal of King Saud University - Science

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Many regions of the world, including Saudi Arabia, are medically vulnerable by the spread of leishmaniasis. Although the effectiveness, the current available drugs suffer from the appearance of resistant strains in epidemic areas and their toxic side-effects. We report the use of the iron chelator deferoxamine (DFRX) that can be used as antileishmanial agents. Our experimental procedure was to follow up the growth of Leishmania major stages (extracellular promastigotes, exinic extracellular amastigotes and intracellular amastigotes) in presence of the tested compound in the culture media in different concentrations (10 lg/ml, 25 lg/ml, 50 lg/ml and no treatment) and comparing it to the untreated control. The compound showed antileishmanial activities as it showed great activity against the growth of the three Leishmania stages in a time and dose dependent manner. Finally, this compound shows a promising potential activity to be a possible antileishmanial compound alternatively or in combination with the currently used drugs.

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“…Nevertheless, the source of catalytic iron in malaria parasites is still unknown. Both non heme [ 32 , 35 ] and heme iron [ 36 ] were suggested to be able to cleave artemisinin, with respective experimental evidence to support those ideas. Many other studies related to the interaction of iron and artemisinin were also reported [ 37 , 38 , 39 , 40 ].…”

Section: Artemisinins and Ironmentioning

confidence: 97%

Biological Actions of Artemisinin: Insights from Medicinal Chemistry Studies

Zhou

2010

Molecules

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Artemisinins have become essential antimalarial drugs for increasingly widespread drug-resistant malaria strains. Although tremendous efforts have been devoted to decipher how this class of molecules works, their exact antimalarial mechanism is still an enigma. Several hypotheses have been proposed to explain their actions, including alkylation of heme by carbon-centered free radicals, interference with proteins such as the sarcoplasmic/endoplasmic calcium ATPase (SERCA), as well as damaging of normal mitochondrial functions. Besides artemisinins, other endoperoxides with various backbones have also been synthesized, some of which showed comparable or even higher antimalarial effects. It is noteworthy that among these artemisinin derivatives, some enantiomers displayed similar in vitro malaria killing efficacy. In this article, the proposed mechanisms of action of artemisinins are reviewed in light of medicinal chemistry findings characterized by efficacy-structure studies, with the hope of gaining more insight into how these potent drugs work.

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Iron chelators as drugs against malaria pose a potential risk

Cited by 8 publications

References 25 publications

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases

In vitro evaluation of the efficacy of deferoxamine against Leishmania major life cycle stages

Biological Actions of Artemisinin: Insights from Medicinal Chemistry Studies

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