Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

Fabio Zuccotto, Marketa Zvelebil, Reto Brun, Shafinaz F. Chowdhury, Raffaella Di Lucrezia, Isabel Leal, Louis Maes, Luis M. Ruiz-Perez, Dolores Gonzalez Pacanowska, Ian H . Gilbert (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

Abstract

There is an urgent need for the development of new drugs to treat Chagas' disease, which is caused by the protozoan parasite Trypanosoma cruzi. The enzyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential drug target for Chagas' disease. A homology model of the enzyme was used to search the Cambridge Structural Database using the program DOCK 3.5. Compounds were then tested against the enzyme and the whole parasite. Compounds were also screened against the related parasite, Trypanosoma brucei.

Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume36
Issue number5
DOIs
Publication statusPublished - May 2001

Keywords

  • Animals
  • Cell Line
  • Chagas Disease
  • Databases as Topic
  • Disease Models, Animal
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors
  • Folic Acid Antagonists
  • Inhibitory Concentration 50
  • Mice
  • Muscles
  • Rats
  • Tetrahydrofolate Dehydrogenase
  • Trypanosoma brucei rhodesiense
  • Trypanosoma cruzi
  • Journal Article
  • Research Support, Non-U.S. Gov't

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