Design, synthesis and evaluation of 2,4-diaminoquinazolines as inhibitors of trypanosomal and leishmanial dihydrofolate reductase
| Autor: | Ian H. Gilbert, Dolores González-Pacanowska, Luis M. Ruiz Perez, Didier Pez, Soghra Khabnadideh, Alexander Musso, Reto Brun |
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| Rok vydání: | 2004 |
| Předmět: |
Chagas disease
Models Molecular Trypanosoma brucei rhodesiense Trypanosoma cruzi Clinical Biochemistry Leishmania donovani Antiprotozoal Agents Pharmaceutical Science Trypanosoma brucei Crystallography X-Ray Biochemistry Structure-Activity Relationship Parasitic Sensitivity Tests parasitic diseases Drug Discovery Dihydrofolate reductase medicine Animals Enzyme Inhibitors Molecular Biology biology Molecular Structure Chemistry Organic Chemistry Kinetoplastida biology.organism_classification medicine.disease Tetrahydrofolate Dehydrogenase Enzyme inhibitor Drug Design biology.protein Quinazolines Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry. 13(7) |
| ISSN: | 0968-0896 |
| Popis: | This paper describes the design, synthesis and evaluation of a series of 2,4-diaminoquinazolines as inhibitors of leishmanial and trypanosomal dihydrofolate reductase. Compounds were designed by a generating virtual library of compounds and docking them into the enzyme active site. Following their synthesis, they were found to be potent and selective inhibitors of leishmanial dihydrofolate reductase. The compounds were also found to have potent activity against Trypanosoma brucei rhodesiense, a causative organism of African trypanosomiasis and also against Trypanosoma cruzi, the causative organism of Chagas disease. There was significantly lower activity against Leishmania donovani, one of the causative organisms of leishmaniasis. |
| Databáze: | OpenAIRE |
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