Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase.

@article{McCarthy2009DesignSA,
  title={Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase.},
  author={Orla McCarthy and Alex Musso-Buendia and M Kaiser and Reto Brun and Luis Miguel Ru{\'i}z-P{\'e}rez and Nils Gunnar Johansson and Dolores Gonz{\'a}lez Pacanowska and Ian H. Gilbert},
  journal={European journal of medicinal chemistry},
  year={2009},
  volume={44 2},
  pages={678-88}
}
The ubiquitous enzyme dUTP nucleotidohydrolase (dUTPase) catalyses the hydrolysis of dUTP to dUMP and can be considered as the first line of defence against incorporation of uracil into DNA. Inhibition of this enzyme results in over-incorporation of uracil into DNA, leading to DNA fragmentation and cell death and is therefore lethal. By taking advantage of structural differences between the human and Plasmodium dUTPase, selective inhibitors of the enzyme can be designed and synthesised with the… CONTINUE READING

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