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  • Title: Novel bis- and tris-1,2,4-trioxanes: synthesis and antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice.
    Author: Singh C, Verma VP, Naikade NK, Singh AS, Hassam M, Puri SK.
    Journal: J Med Chem; 2008 Dec 11; 51(23):7581-92. PubMed ID: 19006381.
    Abstract:
    A new series of bis-1,2,4-trioxanes 12a-h, 13a-h, and 14a-h and tris-1,2,4-trioxanes 12i-14i were prepared and evaluated against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. Cyclopentane-based bis-trioxanes 12a, 12b, 12f-h and cyclohexane-based bis-trioxanes 13a, 13f, and 13g showed promising activity. All the tris-1,2,4-trioxanes were found to be inactive. Bis-trioxane 12a, the most active compound of the series, provided 100% and 80% protection to infected mice at 48 and 24 mg/kg x 4 days, respectively. Clinically useful drug beta-arteether provided 100% and 20% protection at similar doses.
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