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[bf]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.
|Original language||English (US)|
|Number of pages||3|
|Journal||Journal of Medicinal Chemistry|
|State||Published - Sep 7 2006|
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery