Abstract
A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.
Highlights
Malaria is the most relevant parasitic disease and, despite the many efforts made to eradicate malaria, the disease still accounts for 0.5 million deaths per year globally (WHO 2015)
Comparison of recrudescence test using Plasmodium berghei (Pb) and PbGFP-infected mice - In view of the importance to observe the rapid decrease of parasitaemia after antimalarial treatment, it was first compared two methodologies used to the test of new antimalarial drugs (Aguiar et al 2012b, de Souza et al 2012)
PbGFP-infected erythrocytes were further counted by flow cytometry and it was observed increased levels of parasitaemia up to day 6 postinfection (Fig. 1C)
Summary
Malaria is the most relevant parasitic disease and, despite the many efforts made to eradicate malaria, the disease still accounts for 0.5 million deaths per year globally (WHO 2015). Several cases of resistance to artemisinin derivatives have been observed, first at the Cambodia-Thailand border (Dondorp et al 2010) and spread across Southeast Asia (Ashley et al 2014) Such a scenario compels the discovery of novel antimalarial drugs. It was demonstrated that the insertion of a ciclohexyl group in hydroxyethylamine core synthesised from alkylamines increase the antimalarial of such molecule (de Souza et al 2012) It was tested newly synthesised nine different hydroxyethylamine derived from ring-opening of the (2S,3S)-Boc-phenylalanine epoxide with benzylamine in refluxing isopropanol, according its antimalarial activity using the mouse in vivo model of infection with green fluorescent protein-expressing Plasmodium berghei (PbGFP)
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