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New tissue schizontocidal antimalarial drugs

D E Davidson, A L Ager, J L Brown

    Bulletin of the World Health Organization
    |January 1, 1981
    PubMed
    Summary
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    New 8-aminoquinoline antimalarials show potent activity against malaria parasites. The compound WR 225448 is a promising radical curative drug, five times more effective than primaquine in preclinical models.

    Area of Science:

    • Medicinal Chemistry
    • Parasitology
    • Drug Discovery

    Background:

    • Antimalarial drug discovery is crucial for combating malaria.
    • Screening of chemical compounds has identified numerous antimalarial candidates.
    • 8-aminoquinolines are known for their activity against exoerythrocytic malaria stages.

    Purpose of the Study:

    • To discover novel causal prophylactic and radical curative antimalarial drugs.
    • To evaluate the efficacy of a new series of 8-aminoquinolines against malaria parasites.
    • To identify potent antimalarial compounds for further development.

    Main Methods:

    • Screening of approximately 4000 chemical compounds in rodent and simian malaria models.
    • Evaluation of causal prophylactic activity using Plasmodium berghei in rodents.

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  • Assessment of radical curative activity against Plasmodium cynomolgi in rhesus monkeys.
  • Testing blood schizontocidal activity against various Plasmodium species and strains.

    • Main Results:

    • Over 700 antimalarial drugs were discovered, with 10 distinct chemical groups showing causal prophylactic activity.
    • Only 6- and 8-aminoquinolines cured persistent exoerythrocytic infections.
    • The novel 4-methyl-5-phenoxy-6-methoxy-8-aminoquinoline series demonstrated potent activity.
    • WR 225448 was 5 times more potent than primaquine in curing P. cynomolgi infections.
    • WR 225448 showed broad-spectrum blood schizontocidal activity, including against drug-resistant P. falciparum.

    Conclusions:

    • A new series of 8-aminoquinolines, including WR 225448, are potent antimalarial drugs.
    • WR 225448 is a highly effective radical curative agent with broad-spectrum activity.
    • Further investigation into WR 225448 is warranted, considering its efficacy and toxicity profile.