Design, synthesis and antimalarial activity of a glyoxylylhydrazone library

  • Bioorg Med Chem Lett. 2004 Sep 6;14(17):4439-43. doi: 10.1016/j.bmcl.2004.06.056.
A Ryckebusch  1 ,  J-S Fruchart ,  L Cattiaux ,  P Rousselot-Paillet ,  V Leroux ,  O Melnyk ,  P Grellier ,  E Mouray ,  C Sergheraert ,  P Melnyk
Affiliations
  • 1. Institut de Biologie et Institut Pasteur de Lille--UMR CNRS 8525--Université de Lille II, 1 rue du Professeur Calmette, BP 447, 59021, France.
PMID: 15357968 DOI: 10.1016/j.bmcl.2004.06.056
Abstract

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.