Urea-based inhibitors of Trypanosoma brucei methionyl-tRNA synthetase: selectivity and in vivo characterization.

@article{Shibata2012UreabasedIO,
  title={Urea-based inhibitors of Trypanosoma brucei methionyl-tRNA synthetase: selectivity and in vivo characterization.},
  author={Sayaka Shibata and J Robert Gillespie and Ranae M. Ranade and Cho Yeow Koh and Jessica E. Kim and Joy U Laydbak and Frank Zucker and Wim G. J. Hol and Christophe L. M. J. Verlinde and Frederick S Buckner and Erkang Fan},
  journal={Journal of medicinal chemistry},
  year={2012},
  volume={55 14},
  pages={
          6342-51
        }
}
Urea-based methionyl-tRNA synthetase inhibitors were designed, synthesized, and evaluated for their potential toward treating human African trypanosomiasis (HAT). With the aid of a homology model and a structure-activity-relationship approach, low nM inhibitors were discovered that show high selectivity toward the parasite enzyme over the closest human homologue. These compounds inhibit parasite growth with EC(50) values as low as 0.15 μM while having low toxicity to mammalian cells. Two… CONTINUE READING

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