Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening

Juan Alberto Castillo-Garit, Oremia Del Toro-Cortés, Maria C. Vega, Miriam Rolón, Antonieta Rojas De Arias, Gerardo M. Casañola-Martin, José A. Escario, Alicia Gómez-Barrio, Yovani Marrero-Ponce, Francisco Torrens, Concepción Abad

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

20 Citas (Scopus)

Resumen

Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structureeactivity relationship study to identify new trypanosomicidal compounds. A data set of 440 organic chemicals, 143 with antitrypanosomal activity and 297 having other clinical uses, is used to develop the theoretical models. Two discriminant models, computed using bondbased bilinear indices, are developed and both show accuracies higher than 86% for training and test sets. The stochastic model correctly indentifies nine out of eleven compounds of a set of organic chemicals obtained from our synthetic collaborators. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Both models show a good agreement between theoretical predictions and experimental results. Three compounds showed IC50 values for epimastigote elimination (AE) lower than 50 μM, while for the benznidazole the IC50 = 54.7 μM which was used as reference compound. The value of IC50 for cytotoxicity of these compounds is at least 5 times greater than their value of IC50 for AE. Finally, we can say that, the present algorithm constitutes a step forward in the search for efficient ways of discovering new antitrypanosomal compounds.

Idioma originalInglés
Páginas (desde-hasta)238-244
Número de páginas7
PublicaciónEuropean Journal of Medicinal Chemistry
Volumen96
DOI
EstadoPublicada - 26 may. 2015
Publicado de forma externa

Huella

Profundice en los temas de investigación de 'Bond-based bilinear indices for computational discovery of novel trypanosomicidal drug-like compounds through virtual screening'. En conjunto forman una huella única.

Citar esto