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Antimalarial versus cytotoxic properties of dual drugs derived from 4-aminoquinolines and Mannich bases: Interaction with DNA

The synthesis and biological evaluation of new organic and organometallic dual drugs designed as potential antimalarial agents are reported. A series of 4-aminoquinoline-based Mannich bases with variations in the aliphatic amino side chain were prepared via a three-steps synthesis. These compounds w...

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Main Authors: Wenzel, Nicole (Author) , Chavain, Natascha (Author) , Wang, Yulin (Author) , Friebolin, Wolfgang (Author) , Maes, Louis (Author) , Pradines, Bruno (Author) , Lanzer, Michael (Author) , Yardley, Vanessa (Author) , Brun, Reto (Author) , Herold-Mende, Christel (Author) , Biot, Christophe (Author) , Tóth, Katalin (Author) , Davioud-Charvet, Elisabeth (Author)
Format: Article (Journal)
Language:English
Published: 22 April 2010
In: Journal of medicinal chemistry
Year: 2010, Volume: 53, Issue: 8, Pages: 3214-3226
ISSN:1520-4804
DOI:10.1021/jm9018383
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/jm9018383
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Author Notes:Nicole I. Wenzel, Natascha Chavain, Yulin Wang, Wolfgang Friebolin, Louis Maes, Bruno Pradines, Michael Lanzer, Vanessa Yardley, Reto Brun, Christel Herold-Mende, Christophe Biot, Katalin Tóth, and Elisabeth Davioud-Charvet
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Summary:The synthesis and biological evaluation of new organic and organometallic dual drugs designed as potential antimalarial agents are reported. A series of 4-aminoquinoline-based Mannich bases with variations in the aliphatic amino side chain were prepared via a three-steps synthesis. These compounds were also tested against chloroquine-susceptible and chloroquine-resistant strains of Plasmodium falciparum and assayed for their ability to inhibit the formation of β-hematin in vitro using a colorimetric β-hematin inhibition assay. Several compounds showed a marked antimalarial activity, with IC50 and IC90 values in the low nM range but also a high cytotoxicity against mammalian cells, in particular a highly drug-resistant glioblastoma cell line. The newly designed compounds revealed high DNA binding properties, especially for the GC-rich domains. Altogether, these dual drugs seem to be more appropriate to be developed as antiproliferative agents against mammalian cancer cells than Plasmodium parasites.
Item Description:Gesehen am 16.11.2023
Physical Description:Online Resource
ISSN:1520-4804
DOI:10.1021/jm9018383

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