Iron chelators and malaria

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  • #175
    Dan S
    Keymaster

    Below are a few papers on iron chelators as malaria treatment. Iron chelators have been researched a great deal for use in malaria, but to my knowledge have not been developed into any marketed drugs.

    But the fact that iron chelators are a known and well-established category of malaria active chemicals is certainly interesting, and I think lends support to taking IP6 and minimizing iron intake.

     

    Working on getting this paper:

    Drug Metab Rev. 2009;41(4):644-62. doi: 10.1080/03602530903178905.
    Malaria and iron: history and review.
    Weinberg ED, Moon J.
    Source

    Department of Biology and Program in Medical Sciences, Indiana University, Bloomington, Indiana, USA.
    Abstract

    To cause infection, nearly all protozoa, fungi, and bacteria must obtain growth-essential iron from their hosts. To suppress infection, hosts have evolved iron-withholding defense systems. Enhancement of iron withholding is a potential target for the development of novel therapeutic agents. This review focuses on the association of iron with current and emerging antimalarial drugs. Proposed mechanisms of antimalarial action of (1) iron-requiring agents, the artemisinins, are compared with (2) a spectrum of compounds that withdraw iron by chelation. A novel approach to malarial chemotherapy might involve the sequential use of a member of each of the two categories.

     

     

    Med Chem. 2006 Mar;2(2):133-8.
    Design, synthesis and antimalarial activity of a new class of iron chelators.
    Solomon VR, Haq W, Puri SK, Srivastava K, Katti SB.
    Source

    Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow 226 001, India.
    Abstract

    Iron is crucial for many biochemical reactions involved in the growth and multiplication of the malaria parasite Plasmodium falciparum. There are many reports indicating that the iron chelators have antimalarial activity in vitro, in vivo and in human studies. However, these compounds suffer from a number of serious problems such as limited membrane permeability, short half-life and require long subcutaneous infusions. To circumvent these drawbacks we have designed a new class of iron chelators, wherein EDTA is tethered to 4-aminoquinoline. Here 4-aminoquinoline scaffold is used as a carrier to penetrate biological membrane and facilitate targetting the compounds to acidic food vacuole of the parasite. This study describes the synthesis of novel iron chelators and their in vitro antimalarial activity against P. falciparum strain of NF-54. The calculated LogP values of these compounds suggest the importance of lipophilicity for the antimalarial activity. The EDTA esters are more active than the corresponding acids. The biophysical studies suggest that these compounds may inhibit the parasite growth by iron chelation mechanism.

    • This topic was modified 8 years, 5 months ago by Dan S.
    • This topic was modified 8 years, 5 months ago by Dan S.
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    #296
    Charles
    Member

    So is the EDTA, 4-aminoquinoline combo available for purchase? Im guessing it connects to iron more than regular EDTA- which has a relatively low affinity for iron.

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