Design, synthesis, and characterization of novel aminoalcohol quinolines with strong in vitro antimalarial activity

Malaria is the fifth most lethal parasitic infections in the world. Herein, five new series of aminoalcohol quinolines including fifty-two compounds were designed, synthesized and evaluated in vitro against Pf3D7 and PfW2 strains. Among them, fourteen displayed IC50 values below or near of 50.0 nM whatever the strain with selectivity index often superior to 100.17b was found as a promising antimalarial candidate with IC50 values of 14.9 nM and 11.0 nM against respectively Pf3D7 and PfW2 and a selectivity index higher than 770 whatever the cell line is. Further experiments were achieved to confirm the safety and to establish the preliminary ADMET profile of compound 17b before the in vivo study performed on a mouse model of P. berghei ANKA infection. The overall data of this study allowed to establish new structure-activity relationships and the development of novel agents with improved pharmacokinetic properties. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

This study designed, synthesized, and evaluated five new series of aminoalcohol quinolines against Pf3D7 and PfW2 strains in vitro. Among the compounds, fourteen showed promising activity with IC50 values below or near 50.0 nM and high selectivity index. Compound 17b exhibited potent antimalarial activity with IC50 values of 14.9 nM and 11.0 nM against Pf3D7 and PfW2, respectively, and a high selectivity index. Further experiments and in vivo studies are needed to confirm its safety and efficacy.