The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase

Fabio Zuccotto, Reto Brun, Dolores Gonzalez Pacanowska, Luis M. Ruiz Perez, Ian H. Gilbert (Lead / Corresponding author)

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This paper describes the design and synthesis of potential inhibitors of Trypanosoma cruzi dihydrofolate reductase using a structure-based approach. A model of the structure of the T cruzi enzyme was compared with the structure of the human enzyme. The differences were used to design modifications of methotrexate to produce compounds which should be selective for the parasite enzyme. The derivatives of methotrexate were synthesised and tested against the enzyme and intact parasites. (C) 1999 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)1463-1468
Number of pages6
JournalBioorganic & Medicinal Chemistry Letters
Issue number10
Publication statusPublished - 17 May 1999


  • Animals
  • Binding Sites
  • Cell Line
  • Drug Design
  • Enzyme Inhibitors
  • Folic Acid Antagonists
  • Humans
  • Mice
  • Molecular Structure
  • Recombinant Proteins
  • Tetrahydrofolate Dehydrogenase
  • Trypanosoma cruzi
  • Journal Article
  • Research Support, Non-U.S. Gov't

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