A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum

Steven J. Burgess; Audrey Selzer; Jane Xu Kelly; Martin J. Smilkstein; Michael K. Riscoe; David H. Peyton

doi:10.1021/jm060399n

A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum

Steven J. Burgess, Audrey Selzer, Jane Xu Kelly, Martin J. Smilkstein, Michael K. Riscoe, David H. Peyton

Research output: Contribution to journal › Article › peer-review

129 Scopus citations

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[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)
Pages (from-to)	5623-5625
Number of pages	3
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	18
DOIs	https://doi.org/10.1021/jm060399n
State	Published - Sep 7 2006
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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title = "A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum",

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[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.",

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AU - Burgess, Steven J.

AU - Selzer, Audrey

AU - Kelly, Jane Xu

AU - Smilkstein, Martin J.

AU - Riscoe, Michael K.

AU - Peyton, David H.

PY - 2006/9/7

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AB - 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.

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A chloroquine-like molecule designed to reverse resistance in Plasmodium falciparum

Abstract

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