Structure-activity relationships for a class of selective inhibitors of the major cysteine protease from Trypanosoma cruzi |
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| Authors: | Rafael V. C. Guido Gustavo H. G. Trossini Marcelo S. Castilho Glaucius Oliva Elizabeth I. Ferreira |
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| Affiliation: | 1. Laboratório de Química Medicinal e Computacional, Centro de Biotecnologia Molecular Estrutural, Instituto de Física de S?o Carlos, Universidade de S?o Paulo, Av. Trabalhador S?o-carlense 400S?o Carlos-SP, 13560-970, Brazil;2. Laboratório de Planejamento e Síntese de Quimioterápicos Potenciais Contra Endemias Tropicais, Faculdade de Ciências Farmacêuticas, Universidade de S?o Paulo, Av. Professor Lineu Prestes 580S?o Paulo-SP, 05508-900, Brazil;3. Laboratório de Bioinformática e Modelagem Molecular, Faculdade de Farmácia, Universidade Federal da Bahia, Campus Universitário de OndinaSalvador-BA, 40170-290, Brazil |
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| Abstract: | Chagas' disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. Cruzain, the major cysteine protease from Trypanosoma cruzi, is an attractive target for antitrypanosomal chemotherapy. In the present work, classical two-dimensional quantitative structure-activity relationships (2D QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 45 thiosemicarbazone and semicarbazone derivatives as inhibitors of T. cruzi cruzain. Significant statistical models (HQSAR, q2 = 0.75 and r2 = 0.96; classical QSAR, q2 = 0.72 and r2 = 0.83) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 10 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR,   | |
| Keywords: | Chagas' disease enzyme inhibitors drug design chemotherapy QSAR |
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