Journal of medicinal and pharmaceutical chemistry 2008-10-09

New chimeric antimalarials with 4-aminoquinoline moiety linked to a tetraoxane skeleton.

Igor Opsenica, Dejan Opsenica, Charlotte Anne Lanteri, Lalaine Anova, Wilbur K Milhous, Kirsten S Smith, Bogdan A Solaja

Index: J. Med. Chem. 51(19) , 6216-9, (2008)

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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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