Parasite-Mediated Degradation of Synthetic Ozonide Antimalarials Impacts In Vitro Antimalarial Activity

No abstract is available for this paper.

• Publication year

  2017

• Venue

  Antimicrobial Agents and Chemotherapy

• Publication date

  2017-12-20

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1128/AAC.01566-17PMID 29263074PMCID PMC5826100
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2016influential reference
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  2016influential reference
• K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates

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  2014cited by this paper
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• Spread of artemisinin resistance in Plasmodium falciparum malaria.

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  2014cited by this paper
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  2013influential reference
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  2013influential reference
• A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

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  2011influential reference
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  2011influential reference
• Pharmacokinetics and Pharmacodynamics of Arterolane Maleate Following Multiple Oral Doses in Adult Patients With P. falciparum Malaria

  2011cited by this paper
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  2010cited by this paper
• Guidelines for the treatment of malaria

  2010cited by this paper
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• Artemisinin Directly Targets Malarial Mitochondria through Its Specific Mitochondrial Activation

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• Artemisinin resistance in Plasmodium falciparum malaria.

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  2009cited by this paper
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  2009cited by this paper
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  2008influential reference
• Relationship between Antimalarial Activity and Heme Alkylation for Spiro- and Dispiro-1,2,4-Trioxolane Antimalarials

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• In vitro assessment of the pharmacodynamic properties of DB75, piperaquine, OZ277 and OZ401 in cultures of Plasmodium falciparum.

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• Peroxide Bond-Dependent Antiplasmodial Specificity of Artemisinin and OZ277 (RBx11160)

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• Chemical kinetics and aqueous degradation pathways of a new class of synthetic ozonide antimalarials.

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• Bioavailable iron and heme metabolism in Plasmodium falciparum.

  2005cited by this paper
• Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(II).

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• Spiro and dispiro-1,2,4-trioxolanes as antimalarial peroxides: charting a workable structure-activity relationship using simple prototypes.

  2005cited by this paper
• Simple and Inexpensive Fluorescence-Based Technique for High-Throughput Antimalarial Drug Screening

  2004cited by this paper
• Cysteine proteases of malaria parasites.

  2004cited by this paper
• Recrudescence in artesunate-treated patients with falciparum malaria is dependent on parasite burden not on parasite factors.

  2003cited by this paper
• The Chelatable Iron Pool in Living Cells: A Methodically Defined Quantity

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• Inoculum effect leads to overestimation of in vitro resistance for artemisinin derivatives and standard antimalarials: a Gambian field study

  1999influential reference
• Hemoglobin metabolism in the malaria parasite Plasmodium falciparum.

  1997cited by this paper
• In vitro stage-specific sensitivity of Plasmodium falciparum to quinine and artemisinin drugs.

  1996cited by this paper
• Iron Acquired from Transferrin by K562 Cells Is Delivered into a Cytoplasmic Pool of Chelatable Iron(II) (*)

  1995cited by this paper
• Mechanism-based design, synthesis, and in vitro antimalarial testing of new 4-methylated trioxanes structurally related to artemisinin: the importance of a carbon-centered radical for antimalarial activity.

  1994cited by this paper
• Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu)

  1993cited by this paper
• Hemin-catalyzed decomposition of artemisinin (qinghaosu).

  1992cited by this paper
• Regiospecifically oxygen-18 labeled 1,2,4-trioxane: a simple chemical model system to probe the mechanism(s) for the antimalarial activity of artemisinin (qinghaosu).

  1992cited by this paper
• Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action.

  1991cited by this paper
• Stage specific actions of antimalarial drugs on Plasmodium falciparum in culture.

  1989cited by this paper
• Inoculum effect with chloroquine and Plasmodium falciparum

  1987cited by this paper
• Synchronization of Plasmodium falciparum erythrocytic stages in culture.

  1979cited by this paper
• Human malaria parasites in continuous culture.

  1976cited by this paper

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  2023cites this paper
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  2023cites this paper
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  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
• Ozonide antimalarials alkylate heme in the malaria parasite Plasmodium falciparum.

  2019cites this paper
• Exogenous Iron Increases Fasciocidal Activity and Hepatocellular Toxicity of the Synthetic Endoperoxides OZ78 and MT04

  2019cites this paper
• Ozonide Antimalarial Activity in the Context of Artemisinin-Resistant Malaria.

  2019cites this paper