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  • Title: New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton.
    Author: Opsenica I, Opsenica D, Lanteri CA, Anova L, Milhous WK, Smith KS, Solaja BA.
    Journal: J Med Chem; 2008 Oct 09; 51(19):6216-9. PubMed ID: 18774792.
    Abstract:
    The synthesis of the chimeric molecules consisting of two pharmacophores, tetraoxane and 7-chloro-4-aminoquinoline, is reported. The tetraoxanes 2, 4, and 8 show relatively potent in vitro antimalarial activities, with IC90 values for the Plasmodium falciparum strain W2 of 2.26, 12.44, and 10.74 nM, respectively. In addition, two compounds, 2 and 4, cured mice in a modified Thompson test for antimalarial blood stage activity, with a minimum curative dose of 80 mg/kg, a minimum active dose of 20 mg/kg/day, and a maximum tolerated dose of >960 mg/kg.
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