Basic 3-hydroxypyridin-4-ones: Potential antimalarial agents

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 cell...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2008-05, Vol.43 (5), p.1035-1047
Main Authors: Dehkordi, Lotfollah S., Liu, Zu D., Hider, Robert C.
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimalarials - chemical synthesis
Antimalarials - chemistry
Antimalarials - pharmacology
Antiparasitic agents
Biological and medical sciences
Chloroquine - pharmacology
Drug Resistance
Hydroxypyridinones
Iron - metabolism
Iron Chelating Agents - chemical synthesis
Iron Chelating Agents - chemistry
Iron Chelating Agents - pharmacology
Iron chelators
Iron Overload - metabolism
Lysosomotrophic
Malaria
Male
Medical sciences
Parasitic Sensitivity Tests
Pharmacology. Drug treatments
Plasmodium falciparum - drug effects
Pyridones - chemical synthesis
Pyridones - chemistry
Pyridones - pharmacology
Rats
Rats, Wistar
Structure-Activity Relationship
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Summary: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. [Display omitted]
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2007.07.011