DASSONVILLE-KLIMPT, Alexandra; SCHNEIDER, J.; DAMIANI, Céline; TISNERAT, Camille; COHEN, Anita; AZAS, Nadine; MARCHIVIE, Mathieu; GUILLON, J; MULLIÉ, Catherine; AGNAMEY, P.; TOTET, Anne; DORMOI, Jérôme; TAUDON, Nicolas; PRADINES, Bruno; SONNET, Pascal

doi:10.1016/j.ejmech.2021.113981

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DASSONVILLE-KLIMPT, Alexandra
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]

SCHNEIDER, J.
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]

DAMIANI, Céline
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]

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European Journal of Medicinal Chemistry. 2022, vol. 228, p. 113981 (26 p.)

Elsevier

Résumé en anglais

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< Réduire

Mots clés en anglais

Malaria

P. falciparum

antimalarial drug resistance

mefloquine analogs

aminoalcohol quinolines

Malaria

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

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