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 tested compounds exhibited good to excellent antimalarial potency with IC<sub>50</sub> 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.

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Publication Details

Journal
ChemMedChem
Published
2024-12-13
DOI
https://doi.org/10.1002/cmdc.202400790
Citations
2
Primary Topic
Synthesis and Catalytic Reactions
Type
article
Field-Weighted Citation Impact
0.50

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article

Synthesis of New Enantiopure Aminoalcohol Fluorenes as Promising Antimalarial Compounds

Anne Totet, Patrice Agnamey, Romain Mustière, Jean Guillon et al.
2 citations
ChemMedChem
Synthesis and Catalytic Reactions
0.50
article

Synthesis of New Enantiopure Aminoalcohol Fluorenes as Promising Antimalarial Compounds

Anne Totet, Patrice Agnamey, Romain Mustière, Jean Guillon, Camille Tisnerat, Mathieu Marchivie, Céline Damiani, Alexandra Dassonville‐Klimpt, Jérémy Schneider, Pascal Sonnet, René Momha, Aurélie Herrero
article en
2 citations

Abstract

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 IC<sub>50</sub> 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.

ChemMedChemVol. 20(6)
Centre National de la Recherche Scientifique (FR), Université de Bordeaux (FR), Inserm (FR), Institut de Chimie de la Matière Condensée de Bordeaux (FR), Acides nucléiques: Régulations naturelles et artificielles (FR), Agents infectieux, résistance et chimiothérapie (FR), Université de Picardie Jules Verne (FR)
Agence Nationale de la Recherche, Ministère de la Défense, Muséum National d'Histoire Naturelle, Direction Générale de l’Armement
Openalex Percentile: Top 37%
Synthesis and Catalytic Reactions
0.50
DOIOpen Access PDFOpenAlex
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