AI Article Synopsis
- The study reports a simple 2-3 step synthesis of γ-hydroxy-γ-lactam tetramates featuring a 7-chloro-4-aminoquinoline structure and evaluates their effectiveness as potential antimalarial agents.
- The antimalarial activity of these new compounds was tested against different strains of Plasmodium falciparum, showing effectiveness in the range of 14-827nM and generally good resistance indices.
- Additionally, the most promising compounds were found non-toxic to human endothelial cells at concentrations up to 50μM and demonstrated stability in neutral pH conditions for at least 48 hours.
Article Abstract
In this Letter we report on an efficient and short 2-3 steps synthesis of γ-hydroxy-γ-lactam derived-tetramates bearing a 7-chloro-4-aminoquinoline skeleton and their evaluation as potent antimalarials. These molecules were obtained through ring opening-ring closure (RORC) process of γ-ylidene-tetronate derivatives in the presence of 7-chloro-4-aminoquinoline-derived amines. In vitro antimalarial activity of these new γ-lactams was evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and they were found to be active in the range of 14-827nM with generally good resistance index. A preliminary SAR study is also presented to explain these results. Finally, the most active compounds did not show in vitro cytotoxicity when tested against Human Umbilical Vein Endothelial Cells (HUVEC) up to concentration of 50μM and they were stable at pH 7.4 for at least 48h.
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| http://dx.doi.org/10.1016/j.bmcl.2016.09.038 | DOI Listing |
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7-Chloro-4-aminoquinoline γ-hydroxy-γ-lactam derived-tetramates as a new family of antimalarial compounds.
Bioorg Med Chem Lett
November 2016
Université Claude Bernard Lyon 1, Université de Lyon, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires ICBMS (UMR 5246), Equipe "Synthèse de Molécules d'Intérêt Thérapeutique (SMITh)", 43 bd du 11 Novembre 1918, F-69622 Villeurbanne, France. Electronic address:
Article Synopsis
- The study reports a simple 2-3 step synthesis of γ-hydroxy-γ-lactam tetramates featuring a 7-chloro-4-aminoquinoline structure and evaluates their effectiveness as potential antimalarial agents.
- The antimalarial activity of these new compounds was tested against different strains of Plasmodium falciparum, showing effectiveness in the range of 14-827nM and generally good resistance indices.
- Additionally, the most promising compounds were found non-toxic to human endothelial cells at concentrations up to 50μM and demonstrated stability in neutral pH conditions for at least 48 hours.
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