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Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening by João Neres; Mark L. Brewer; Laura Ratier; Horacio Botti; Alejandro Buschiazzo; Philip N. Edwards; Paul N. Mortenson; Michael H. Charlton; Pedro M. Alzari; Alberto C. Frasch; Richard A. Bryce; Kenneth T. Douglas is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening about?
trans-Sialidase from Trypanosoma cruzi (TcTS) has emerged as a potential drug target for treatment of Chagas disease. Here, we report the results of virtual screening for the discovery of novel TcTS inhibitors, which targeted both the sialic acid and sialic acid acceptor sites of this enzyme. A library prepared from the Evotec database of commercially available compounds was screened using the molecular docking program GOLD, following the application of drug-likeness filters. Twenty-three compounds selected from the top-scoring ligands were purchased and assayed using a fluorimetric assay. Novel inhibitor scaffolds, with IC 50 values in the submillimolar range were discovered. The 3-benzothiazol-2-yl-4-phenyl-but-3enoic acid scaffold was studied in more detail, and TcTS inhibition was confirmed by an alternative sialic acid transfer assay. Attempts to obtain crystal structures of these compounds with TcTS proved unsuccessful but provided evidence of ligand binding at the active site.
Who reads Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- João Neres; Mark L. Brewer; Laura Ratier; Horacio Botti; Alejandro Buschiazzo; Philip N. Edwards; Paul N. Mortenson; Michael H. Charlton; Pedro M. Alzari; Alberto C. Frasch; Richard A. Bryce; Kenneth T. Douglas
- Publisher
- Elsevier Science; Elsevier ; Elsevier Ltd.; Elsevier BV (ISSN 0960-894X)
- Published
- 2009
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)