A Chloroquine-like Molecule Designed to Reverse Resistance in Plasmodium falciparum
- 12 August 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (18), 5623-5625
- https://doi.org/10.1021/jm060399n
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.Keywords
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