Discovery of novel Trypanosoma cruzi glyceraldehyde-3-phosphate dehydrogenase inhibitors
Nenhuma Miniatura disponível
Data
2009-03-15
Autores
Freitas, Renato F.
Prokopczyk, Igor M.
Zottis, Aderson
Oliva, Glaucius
Andricopulo, Adriano D.
Trevisan, Maria Teresa S.
Vilegas, Wagner [UNESP]
Silva, Maria Goretti V.
Montanari, Carlos A.
Título da Revista
ISSN da Revista
Título de Volume
Editor
Pergamon-Elsevier B.V. Ltd
Resumo
Based on its essential role in the life cycle of Trypanosoma cruzi, the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been considered a promising target for the development of novel chemotherapeutic agents for the treatment of Chagas' disease. In the course of our research program to discover novel inhibitors of this trypanosomatid enzyme, we have explored a combination of structure and ligand-based virtual screening techniques as a complementary approach to a biochemical screening of natural products using a standard biochemical assay. Seven natural products, including anacardic acids,. avonoid derivatives, and one glucosylxanthone were identified as novel inhibitors of T. cruzi GAPDH. Promiscuous inhibition induced by nonspecific aggregation has been discarded as specific inhibition was not reversed or affected in all cases in the presence of Triton X-100, demonstrating the ability of the assay to find authentic inhibitors of the enzyme. The structural diversity of this series of promising natural products is of special interest in drug design, and should therefore be useful in future medicinal chemistry efforts aimed at the development of new GAPDH inhibitors having increased potency. (C) 2009 Elsevier Ltd. All rights reserved.
Descrição
Palavras-chave
Chagas' disease, Trypanosoma cruzi, GAPDH inhibitors, LBVS, SBVS
Como citar
Bioorganic & Medicinal Chemistry. Oxford: Pergamon-Elsevier B.V. Ltd, v. 17, n. 6, p. 2476-2482, 2009.