Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

There is an urgent need for the development of new drugs to treat Chagas' d isease, which is caused by the protozoan parasite Trypanosoma cruzi. The en zyme dihydrofolate reductase (DHFR) has been a very successful drug target in a number of diseases and we decided to investigate it as a potential dru g target for Chagas' disease. A homology model of the enzyme was used to se arch the Cambridge Structural Database using the program DOCK 3.5. Compound s were then tested against the enzyme and the whole parasite. Compounds wer e also screened against the related parasite, Trypanosoma brucei. (C) 2001 Editions scientifiques et medicales Elsevier SAS.