Design, synthesis and antimalarial activity of a glyoxylylhydrazone library.
Synthesis of a new family of quinolylhydrazone derivatives and evaluation of their activity against a chloroquine-resistant strain of Plasmodium falciparum are described. The best compound displayed an activity 6-fold higher than chloroquine. None of the active compounds were found to inhibit beta-hematin formation in vitro in the same range as chloroquine and five among them displayed lower calculated vacuolar accumulation ratios, suggesting the implication of a different mechanism of action.
Ryckebusch
A
A
Institut de Biologie et Institut Pasteur de Lille--UMR CNRS 8525--Université de Lille II, 1 rue du Professeur Calmette, BP 447, 59021, France.
Fruchart
J-S
JS
Cattiaux
L
L
Rousselot-Paillet
P
P
Leroux
V
V
Melnyk
O
O
Grellier
P
P
Mouray
E
E
Sergheraert
C
C
Melnyk
P
P
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D006038:Glyoxylates / Q000138:chemical synthesis* / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development
D000962:Antimalarials; D006038:Glyoxylates; D006835:Hydrazones; C031150:glyoxylic acid