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A primaquine-chloroquine hybrid with dual activity against Plasmodium liver and blood stages

Lödige, Melanie and Lewis, Matthew D. and Paulsen, Eleonora S. and Esch, Harald L. and Pradel, Gabriele and Lehmann, Leane and Brun, Reto and Bringmann, Gerhard and Mueller, Ann-Kristin. (2013) A primaquine-chloroquine hybrid with dual activity against Plasmodium liver and blood stages. International journal of medical microbiology, Vol. 303, H. 8. pp. 539-547.

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Official URL: http://edoc.unibas.ch/dok/A6205640

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Abstract

We present a new class of hybrid molecules consisting of the established antiplasmodial drugs primaquine and chloroquine. No drug is known to date that acts comparably against all stages of Plasmodium in its life cycle. Starting from available precursors, we designed and synthesized a new-generation compound consisting of both primaquine and chloroquine components, with the intent to produce agents that exhibit bioactivity against different stages of the parasite's life cycle. In vitro, the hybrid molecule 3 displays activity against both asexual and sexual P. falciparum blood stages as well as P. berghei sporozoites and liver stages. In vivo, the hybrid elicits activity against P. berghei liver and blood stages. Our results successfully validate the concept of utilizing one compound to combine different modes of action that attack different Plasmodium stages in the mammalian host. It is our hope that the novel design of such compounds will outwit the pathogen in the spread of drug resistance. Based on the optimized synthetic pathway, the compound is accessible in a smooth and versatile way and open for potential further molecular modification.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Brun, Reto
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Elsevier
ISSN:1438-4221
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 Jan 2014 09:49
Deposited On:31 Jan 2014 09:49

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