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Optimized Griess Reaction for UV-Vis and Naked-eye Determination of Anti-malarial Primaquine
Published on: October 11, 2019
Selection of a trioxaquine as an antimalarial drug candidate
Frédéric Coslédan1, Laurent Fraisse, Alain Pellet
1Palumed, Rue Pierre et Marie Curie, BP 28262, F-31682 Labège Cedex, France.
Abstract:
Trioxaquines are antimalarial agents based on hybrid structures with a dual mode of action. One of these molecules, PA1103/SAR116242, is highly active in vitro on several sensitive and resistant strains of Plasmodium falciparum at nanomolar concentrations (e.g., IC(50) value = 10 nM with FcM29, a chloroquine-resistant strain) and also on multidrug-resistant strains obtained from fresh patient isolates in Gabon. This molecule is very efficient by oral route with a complete cure of mice infected with chloroquine-sensitive or chloroquine-resistant strains of Plasmodia at 26-32 mg/kg. This compound is also highly effective in humanized mice infected with P. falciparum. Combined with a good drug profile (preliminary absorption, metabolism, and safety parameters), these data were favorable for the selection of this particular trioxaquine for development as drug candidate among 120 other active hybrid molecules.
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