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• W2041630103 abstract "Iron is an essential growth component in all living organisms and plays a central role in numerous biochemical processes due to its redox potential and high affinity for oxygen. The use of iron chelators has been suggested as a novel therapeutic approach towards parasitic infections, such as malaria, sleeping sickness and leishmaniasis. Known iron chelating agents such as Deferoxamine and the 3-hydroxypyridin-4-one (HPO) Deferiprone possess anti-parasitic activity but suffer from mammalian toxicity, relatively modest potency, and/or poor oral availability. In this study, we have developed novel derivatives of Deferiprone with increased anti-parasitic activity and reduced cytotoxicity against human cell lines. Of particular interest are several new derivatives in which the HPO scaffold has been conjugated, via a linker, to the 4-aminoquinoline ring system present in the known anti-malaria drug Chloroquine. We report the inhibitory activity of these novel analogues against four parasitic protozoa, Trypanosoma brucei, Trypanosoma cruzi, Leishmania infantum and Plasmodium falciparum, and, for direct comparison, against human cells lines. We also present data, which support the hypothesis that iron starvation is the major cause of growth inhibition of these new Deferiprone–Chloroquine conjugates in T. brucei." @default.
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• W2041630103 date "2013-02-01" @default.
• W2041630103 modified "2023-09-23" @default.
• W2041630103 title "Conjugation to 4-aminoquinoline improves the anti-trypanosomal activity of Deferiprone-type iron chelators" @default.
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• W2041630103 doi "https://doi.org/10.1016/j.bmc.2012.11.009" @default.
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• W2041630103 hasPublicationYear "2013" @default.
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