Synthesis of New Enantiopure Aminoalcohol Fluorenes as Promising Antimalarial Compounds.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2024-12-13 DOI:10.1002/cmdc.202400790

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

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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 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.

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.