ArticleFuture medicinal chemistry2012
Ferrous iron-dependent delivery of therapeutic agents to the malaria parasite.
Article in Future medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Review
- Ferrous iron-activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors.The Journal of experimental medicine · 2022Article
- Drug delivery to the malaria parasite using an arterolane-like scaffold.ChemMedChem · 2015Article
- Efficient and stereocontrolled synthesis of 1,2,4-trioxolanes useful for ferrous iron-dependent drug delivery.Organic letters · 2014Article
- Ferrous iron-dependent drug delivery enables controlled and selective release of therapeutic agents in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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Authors and funding
4 authors.
Funding
Abstract
backgroundThe malaria parasites Plasmodium falciparum and Plasmodium vivax generate significant concentrations of free unbound ferrous iron heme as a side product of hemoglobin degradation. The presence of these chemically reactive forms of iron, rare in healthy cells, presents an opportunity for parasite-selective drug delivery. Accordingly, our group is developing technologies for the targeted delivery of therapeutics to the intra-erythrocytic malaria parasite. These so-called 'fragmenting hybrids' employ a 1,2,4-trioxolane ring system as an iron(II)-sensing 'trigger' moiety and a 'traceless' retro-Michael linker to which a variety of partner drug species may be attached. After ferrous iron-promoted activation in the parasite, the partner drug is released via a β-elimination reaction.
methodsIn this report, we describe three orthogonal experimental approaches that were explored in order to generate in vitro proof-of-concept for ferrous iron-dependent drug delivery from a prototypical fragmenting hybrid.
conclusionStudies of two fragmenting hybrids by orthogonal approaches confirm that a partner drug species can be delivered to live P. falciparum parasites. A key advantage of this approach is the potential to mask a partner drug's intrinsic bioactivity prior to release in the parasite.
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