Biodereplication approach for antimalarial drugs in complex extracts mixtures: active compounds from the insect Pyrrhocoris apterus

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Beniddir, M
Cojean, S
Figadere, B
Loiseau, P
Maciuk, A
Suyyagh-Albouz, S
Vasquez-Ocmin, P
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Malaria remains the most important global public health problem, with an estimated 214 million cases and 438 000 deaths in 2015, principally under 5-years old children [1]. Antimalarial drugs resistance permanent rising calls for new active molecules research against Plasmodium. The principal antimalarial drugs mechanism consists in interrupted heme crystallization in parasite erythrocytic phase, perturbating his waste-sorting strategy [2]. With a target-based approach, we developed a method which identifies heme-active molecule adduct in a complex extract (m/z for heme = 616) by mass spectroscopy (Q-TOF MS). This in vitro miniaturized biodereplication is based on a medium mimicking the parasite digestive vacuole (pH = 4.8) [3]. Application of the method was realized on a methanolic extract of Pyrrhocoris apterus insect (Pyrrhocoridae) (IC50 of extract = 80 ng/mL, Plasmodium falciparum 3D7 chloroquine-sensible strain). Active compounds were identified by m/z adduct (X + 616) using molecular networking4. Successive fractionation of active fractions was performed by several chromatography methods and structural identification was performed by 600 MHz NMR.
Consejo Nacional de Ciencia y Tecnología (CONCYTEC) is acknowledged for PhD funding of Pedro Vásquez-Ocmín; Karine Leblanc for supporting in MS analyses.
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