Molecular and physiologic basis of quinoline drug resistance in Plasmodium falciparum malaria
- PMID: 19416013
- PMCID: PMC2724744
- DOI: 10.2217/fmb.09.15
Molecular and physiologic basis of quinoline drug resistance in Plasmodium falciparum malaria
Abstract
30 years before the discovery of the pfcrt gene, altered cellular drug accumulation in drug-resistant malarial parasites had been well documented. Heme released from catabolized hemoglobin was thought to be a key target for quinoline drugs, and additional modifications to quinoline drug structure in order to improve activity against chloroquine-resistant malaria were performed in a few laboratories. However, parasite cell culture methods were still in their infancy, assays for drug susceptibility were not well standardized, and the power of malarial genetics was decades away. The last 10 years have witnessed explosive progress in elucidation of the biochemistry of chloroquine resistance. This review briefly summarizes that progress, and discusses where additional work is needed.
Conflict of interest statement
Work in the Roepe laboratory has been supported by the NIH (RO1 AI056312, RO1 AI45957, RO1 AI060792, RO1 AI071121, RO1 AI052312), the Burroughs Wellcome foundation, the Luce Foundation and the USA Department of Defense. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
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