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Peroxides as oxidant antimalarials.

J L Vennerstrom1, N Acton, A J Lin

  • 1Department of Medicinal Chemistry, Walter Reed Army Institute of Research, Washington, DC 20307.

Drug Design and Delivery
|January 1, 1989
PubMed
Summary
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Researchers investigated peroxides for antimalarial activity. While several compounds showed in vitro efficacy against Plasmodium falciparum, none demonstrated in vivo activity in mice against Plasmodium berghei.

Area of Science:

  • Medicinal Chemistry
  • Parasitology
  • Drug Discovery

Background:

  • Peroxides, exemplified by artemisinin, are known for their antimalarial properties.
  • Exploring diverse peroxide structures is crucial for identifying new antimalarial leads.

Purpose of the Study:

  • To evaluate the in vitro and in vivo antimalarial activity of a diverse set of 23 peroxide compounds.
  • To assess the structure-activity relationship of various peroxide subclasses against Plasmodium falciparum and Plasmodium berghei.

Main Methods:

  • In vitro screening of 23 peroxides against Plasmodium falciparum.
  • In vivo testing of the selected peroxides in a mouse model infected with Plasmodium berghei.
  • Chemical characterization of hydroperoxides, dialkyl peroxides, acyl/diacylperoxides, peroxyketals, peroxycarbonates, and endoperoxides.

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Main Results:

  • Several peroxide compounds exhibited reasonable antimalarial potency in vitro against Plasmodium falciparum.
  • None of the tested peroxide compounds demonstrated significant antimalarial activity in vivo against Plasmodium berghei in mice.

Conclusions:

  • The in vitro antimalarial activity of peroxides does not always translate to in vivo efficacy.
  • Further research is needed to optimize peroxide structures for in vivo antimalarial drug development.