Theoretical models for the antitrypanosomal activity of thiosemicarbazone derivatives

• Published in: International journal of quantum chemistry 2012-10, Vol.112 (20), p.3364-3370
• Main Authors: Lozano, N. B. H., Weber, K. C., Honorio, K. M., Guido, R. V. C., Andricopulo, A. D., Da Silva, A. B. F.
• Format: Article
• Language: English
• Subjects: antichagasic activity; DFT; pattern recognition techniques; theoretical studies; thiosemicarbazones
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/qua.24213

Thiosemicarbazones are cruzain inhibitors which have been identified as potential antitrypanosomal agents. In this work, several molecular properties were calculated at the density functional theory (DFT)/B3LYP/6‐311G* level for a set of 44 thiosemicarbazones. Unsupervised and supervised pattern recognition techniques (hierarchical cluster analysis, principal component analysis, kth‐nearest neighbors, and soft independent modeling by class analogy) were used to obtain structure–activity relationship models, which are able to classify unknown compounds according to their activities. The chemometric analyses performed here revealed that 12 descriptors can be considered responsible for the discrimination between high and low activity compounds. Classification models were validated with an external test set, showing that predictive classifications were achieved with the selected variable set. The results obtained here are in good agreement with previous findings from the literature, suggesting that our models can be useful on further investigations on the molecular determinants for the antichagasic activity. © 2012 Wiley Periodicals, Inc. Cruzain inhibitors (thiosemicarbazones) have been identified as potential antitrypanosomal agents. Theoretical studies revealed some molecular properties that can be considered responsible for the discrimination between high and low activity compounds. The results obtained are in good agreement with previous findings from the literature, suggesting that models presented in this study can be useful on further investigations on the molecular determinants for the antichagasic activity.