Design, synthesis, and characterization of novel aminoalcohol quinolines with strong in vitro antimalarial activity
DASSONVILLE-KLIMPT, Alexandra
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
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Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
DASSONVILLE-KLIMPT, Alexandra
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
DORMOI, Jérôme
Vecteurs - Infections tropicales et méditerranéennes [VITROME]
Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] [IRBA]
Institut Hospitalier Universitaire Méditerranée Infection [IHU Marseille]
Vecteurs - Infections tropicales et méditerranéennes [VITROME]
Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] [IRBA]
Institut Hospitalier Universitaire Méditerranée Infection [IHU Marseille]
PRADINES, Bruno
Vecteurs - Infections tropicales et méditerranéennes [VITROME]
Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] [IRBA]
Institut Hospitalier Universitaire Méditerranée Infection [IHU Marseille]
Centre National de Référence du Paludisme [IRBA, Marseille] [CNRP]
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Vecteurs - Infections tropicales et méditerranéennes [VITROME]
Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] [IRBA]
Institut Hospitalier Universitaire Méditerranée Infection [IHU Marseille]
Centre National de Référence du Paludisme [IRBA, Marseille] [CNRP]
Language
en
Article de revue
This item was published in
European Journal of Medicinal Chemistry. 2022, vol. 228, p. 113981 (26 p.)
Elsevier
English Abstract
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 ...Read more >
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 propertiesRead less <
English Keywords
Malaria
P. falciparum
antimalarial drug resistance
mefloquine analogs
aminoalcohol quinolines
Malaria
Origin
Hal imported