Antimalarial Properties of Dunnione Derivatives as NQO2 Substrates

Dunnione, a natural productisolated from the leaves of Streptocarpusdunnii ( Gesneriaceae), acts as a substrate for quinone-reductases that may be associated with its antimalarial properties. Following our exploration of reactive oxygen species-producing compounds such as indolones, as possible new approaches for the research of new ways to treat this parasitosis, we explored derivatives of this natural productand their possible antiplasmodial and antimalarial properties, in vitro and in vivo, respectively. Apart from one compound, all the products testedhad weak to moderate antiplasmodial activities, the best IC50 value being equal to 0.58 µM. In vivo activities in the murine model were moderate (at a dose of 50 mg/kg/mice, five times higher than the dose of chloroquine). These results encourage further pharmacomodulation steps to improve the targeting of the parasitized red blood cells and antimalarial activities.