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Iron chelators with antimalarial activity
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ironjustice@aol.com
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PostPosted: Thu Jun 22, 2006 10:12 pm    Post subject: Iron chelators with antimalarial activity Reply with quote

<<snip>>
these compounds may inhibit the parasite growth by iron chelation
mechanism
<<snip>>

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

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.

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