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

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.

Acknowledgements: Consejo Nacional de Ciencia y Tecnología (CONCYTEC) is acknowledged for PhD funding of Pedro Vásquez-Ocmín; Karine Leblanc for supporting in MS analyses.

Keywords: Biodereplication, Heme, Pyrrhocoris apterus, antiplasmodial drugs.

References:

[1] World Health Organization. World Malaria Report 2015. Geneva: WHO Malaria Programme; 2015 p. 2 – 20. Available from: http://www.who.int/malaria/visual-refresh/en/

[2] Tekwani BL, Walker LA. Targeting the Hemozoin Synthesis Pathway of New Antimalarial Drug Discovery: Technologies for In Vitro β-Hematin Formation Assay. Comb Chem High Throughput Screen 2005; 8: 63 – 79

[3] Wunderlich J, Rohrbach P, Dalton JP. The malaria digestive vacuole. Front Biosci 2012; 4: 1424 – 1448

[4] Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N, Glukhov E, Wodtke A, de Felicio R, Fenner A, Wong WR, Linington RG, Zhang L, Debonsi HM, Gerwick WH, Dorrestein PC. Molecular networking as a dereplication strategy. J Nat Prod 2013; 76: 1686 – 1699

Die Autoren geben an, dass kein Interessenkonflikt besteht.