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

Abstract Two-dimensional bond-based bilinear indices and linear discriminant analysis are used in this report to perform a quantitative structure–activity 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 bond-based 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 IC 50 values for epimastigote elimination (AE) lower than 50 μM, while for the benznidazole the IC 50  = 54.7 μM which was used as reference compound. The value of IC 50 for cytotoxicity of these compounds is at least 5 times greater than their value of IC 50 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.