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. 2010 Jan 28;53(2):916-9.
doi: 10.1021/jm900972u.

Reversal agent and linker variants of reversed chloroquines: activities against Plasmodium falciparum

Simeon Andrews  1 , Steven J Burgess, Deborah Skaalrud, Jane Xu Kelly, David H Peyton
Affiliations

Reversal agent and linker variants of reversed chloroquines: activities against Plasmodium falciparum

Simeon Andrews et al. J Med Chem. .

Abstract

We have shown that "reversed chloroquine molecules" constructed from chloroquine-like and resistance "reversal-agent"-like cores can be powerful drugs against malaria ( J. Med. Chem. 2006 , 49 , 5623 - 5625 ). Several reversed chloroquines are now presented that probe parameters governing the activities against chloroquine-resistant and chloroquine-sensitive malaria strains. The design is tolerant to linker and reversal agent changes, but a piperazinyl group adjacent to the quinoline, at least for the group of compounds studied here, may be detrimental.

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Figures

Figure 1
Figure 1
The IC50 values for CQ and compounds 1 – 13. The grey bars are for the CQS D6 strain, and the black bars are for the CQR Dd2 strain, of P. falciparum malaria.
Figure 2
Figure 2
Piperaquine (1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]-propane).
Chart 1
Chart 1
Variations in the RCQ structure; the RA portions are shown in bold bonds.
See this image and copyright information in PMC

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