Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 43, Issue 5, Pages 1035-1047Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2007.07.011
Keywords
hydroxypyridinones; iron chelators; malaria; lysosomotrophic
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3-Hydroxypyridin-4-ones selectively bind iron under biological conditions and one such compound has found application in the treatment of thalassaemia-linked iron overload. Related molecules have also been demonstrated to possess an antimalarial effect at levels which are non-toxic to mammalian cells. In an attempt to improve the efficiency of such molecules we have investigated the effect of introducing basic nitrogen centres into 3-hydroxypyridin-4-ones in an attempt to achieve targeting to lysosomes and other intracellular acidic vacuoles. Several of the compounds reported in this communication possess enhanced antimalarial activity over that of the simple hydroxypyridinone class. (C) 2007 Elsevier Masson SAS. All rights reserved.
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