Synthesis of New Enantiopure Aminoalcohol Fluorenes as Promising Antimalarial Compounds

Herein, we report the design, synthesis, and characterisation of a new library of enantiopure aminoalcohol fluorenes, as well as their in vitro evaluation for biological properties, including activity against two strains of P. falciparum (3D7 and W2) and cytotoxicity on the HepG2 cell line. All test...

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Published in:ChemMedChem 2024-12, p.e202400790
Main Authors: Tisnerat, Camille, Schneider, Jérémy, Mustière, Romain, Herrero, Aurélie, Momha, René, Damiani, Céline, Agnamey, Patrice, Totet, Anne, Marchivie, Mathieu, Guillon, Jean, Dassonville-Klimpt, Alexandra, Sonnet, Pascal
Format: Article
Language:English
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Summary:Herein, we report the design, synthesis, and characterisation of a new library of enantiopure aminoalcohol fluorenes, as well as their in vitro evaluation for biological properties, including activity against two strains of P. falciparum (3D7 and W2) and cytotoxicity on the HepG2 cell line. All tested compounds exhibited good to excellent antimalarial potency with IC50 values ranging from 0.7 to 70.2 nM whatever the strain. Interestingly, most compounds showed equal or better antimalarial activity compared to the reference drugs lumefantrine, mefloquine and chloroquine. Despite moderate cytotoxicity in the micromolar range, all aminoalcohol fluorenes displayed an excellent selectivity index higher than 100 due to strong antimalarial activity. Furthermore, we report in silico analyses of physicochemical and pharmacokinetic properties for all compounds, highlighting the drug-likeness of compound 10 and its promising potential for further studies.
ISSN:1860-7187