Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

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.

The Multistage Antimalarial Compound Calxinin Perturbates P. falciparum Ca2+ Homeostasis by Targeting a Unique Ion Channel

“…Piperazine analogs with medicinal value were previously used to build several potent antimalarial agents [ 13 , 14 , 19 , 20 , 27 , 76 ]. The biological activities of HEA analogs have been extensively studied for their antimalarial activity by our team [ 13 , 14 , 19 , 20 , 27 ] and others [ 77 , 78 , 79 ]. For instance, the HEA analog KAF156 is currently in Phase 2 clinical trials for treating malaria [ 6 ].…”

Synthesis, Antiproliferative and Antimalarial Activities of Dinuclear Silver(I) Complexes with Triphenylphosphine and Thiosemicarbazones Ligands

“…Meanwhile, the presence of a methoxy group at the -meta position in P6 caused a higher SI value of 0.393 than that of P3. Based on the results of previous studies, the insertion of methyl [28] and hydroxyl [29][30] groups into the compounds enhanced the antiplasmodial activity. Nonetheless, it remained uncertain for the role of each functional group in improving the selectivity of the silver complexes.…”