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  • Title: A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum.
    Author: Burgess SJ, Selzer A, Kelly JX, Smilkstein MJ, Riscoe MK, Peyton DH.
    Journal: J Med Chem; 2006 Sep 07; 49(18):5623-5. PubMed ID: 16942036.
    Abstract:
    A class of hybrid molecules which we term 'reversed chloroquines' (RCQs) was designed, and a prototype molecule, N'-(7-chloroquinolin-4-yl)-N-[3-(10,11-dihydrodibenzo[b,f]azepin-5-yl)propyl]-N-methylpropane-1,3-diamine (1), was synthesized and tested against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. An in vitro assay against the two strains indicated that 1 was effective at low-nM concentrations against both strains. A preliminary study in mice demonstrated oral efficacy against P. chabaudi and the absence of obvious toxicity. The RCQ approach therefore appears to be feasible.
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