Design, synthesis and in vitro antimalarial activity of an acylhydrazone library.
A library of acylhydrazone iron chelators was synthesized and tested for its ability to inhibit the growth of a chloroquine-resistant strain of Plasmodium falciparum. Some of these new compounds are significantly more active than desferrioxamine DFO, the iron chelator in widespread clinical use and also than the most effective chelators.
Melnyk
Patricia
P
Institut de Biologie et Institut Pasteur de Lille, UMR CNRS 8525, Université de Lille II, 1 rue du Professeur Calmette, BP 447, 59021 Lille, France. patricia.melnyk@ibl.fr
Leroux
Virginie
V
Sergheraert
Christian
C
Grellier
Philippe
P
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002614:Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003676:Deferoxamine / Q000737:chemistry; D015195:Drug Design; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007501:Iron / Q000737:chemistry; D008956:Models, Chemical; D010963:Plasmodium falciparum / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods*
D000962:Antimalarials; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D006835:Hydrazones; D007501:Iron; D003676:Deferoxamine