Predicción de la actividad anti-Trypanosoma brucei rhodesiense de un grupo de 3,5-Difenilisoxazoles dicationicos por medio de la Topología Molecular
- Karla Vasco Aguas
- Elena Barrio Miguel
- Carmen Ferrando Hernández
- María Alvarez Izquierdo
- Jorge Gálvez Álvarez
- Ramón García Domenech
ISSN: 1697-4298, 0034-0618
Year of publication: 2017
Volume: 83
Issue: 2
Pages: 241-250
Type: Article
More publications in: Anales de la Real Academia Nacional de Farmacia
Abstract
: Currently, there are more than 65 million people at risk of contracting sleeping sickness caused by Trypanosoma brucei. Available treatments for this parasitic disease are limited and have side effects. There is a necessity to investigate novel, effective compounds that also yield low in toxicity. Quantitative StructureActivity Relationship models (QSAR) have been used in this study for predicting anti-Trypanosoma brucei activity and potency in a group of dicationic 3,5- Diphenylisoxazoles. Linear Discriminant Analysis (LDA) correctly classified anti-Trypanosoma brucei activity in 100 % of cases (sensitivity) and inactivity in 86.7 % (specificity). Theoretical bioactivity (pIC50) of the studied compounds was predicted using Multilinear Regression Analysis (MLRA), demonstrating a high correlation between in vitro and in silico results (r2=0.82). Topologic models obtained with LDA and MLRA were applied to the screening of a group of dicationic analogs which presented a high in silico activity. These compounds when selected for in vitro analysis could reduce both time and costs in future drug research.