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Deoxyuridine Triphosphate Nucleotidohydrolase as a drug target against Malaria

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Novel malaria inhibitors

Malaria treatment is in urgent need of novel drugs in order to overcome existing drug resistance issues. A European consortium addressed this problem by inhibiting parasite division.


As part of a Fifth Framework Programme (FP5)-funded project, partners had discovered novel inhibitors of the enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) from Plasmodium falciparum. This enzyme is involved in genome replication of the parasite so inhibiting its action would block Plasmodium falciparum division. The aim of the Plasmodiumdutpase project was to further optimise these early molecules to generate pre-clinical drug candidates. Scientists used the structure and three-dimensional (3D) active site of the enzyme to design and prepare drug-like inhibiting compounds. These were subsequently evaluated against dUTPase from both Plasmodium falciparum and the human enzyme. The killing efficiency of the compounds was also screened against the intact parasite but at the same time, researchers ensured the drugs were not toxic to mammalian cells. Although optimisation of these compounds is required before they can be clinically applied, the Plasmodiumdutpase drugs present potent and selective inhibitors of the dUTPase enzyme of Plasmodium falciparum leading to arrested growth. These drugs will be beneficial for malaria sufferers and are also believed to overcome resistance problems.

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