The structure-based design and synthesis of selective inhibitors of Trypanosoma cruzi dihydrofolate reductase
| Autor: | Luis M. Ruiz Perez, Dolores Gonzalez Pacanowska, Reto Brun, Ian H. Gilbert, Fabio Zuccotto |
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| Rok vydání: | 1999 |
| Předmět: |
Trypanosoma cruzi
Clinical Biochemistry Pharmaceutical Science Biochemistry Cell Line chemistry.chemical_compound Mice parasitic diseases Drug Discovery Dihydrofolate reductase medicine Animals Humans Binding site Enzyme Inhibitors Amastigote Molecular Biology chemistry.chemical_classification Binding Sites biology Molecular Structure Organic Chemistry biology.organism_classification Recombinant Proteins Tetrahydrofolate Dehydrogenase Enzyme chemistry Enzyme inhibitor Drug Design Antifolate biology.protein Molecular Medicine Folic Acid Antagonists Methotrexate medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 9(10) |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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