Computational identification of chemical compounds with potential anti-Chagas activity using a classification tree
Por:
Castillo-Garit, J, Barigye, S, Pham-the, H, Perez-Donate, V, Torrens, F and Perez-Gimenez, F
Publicada:
2 ene 2021
Ahead of Print:
1 ene 2021
Resumen:
Chagas disease is endemic to 21 Latin American countries and is a great public health problem in that region. Current chemotherapy remains unsatisfactory; consequently the need to search for new drugs persists. Here we present a new approach to identify novel compounds with potential anti-chagasic action. A large dataset of 584 compounds, obtained from the Drugs for Neglected Diseases initiative, was selected to develop the computational model. Dragon software was used to calculate the molecular descriptors and WEKA software to obtain the classification tree. The best model shows accuracy greater than 93.4% for the training set; the tree was also validated using a 10-fold cross-validation procedure and through a test set, achieving accuracy values over 90.5% and 92.2%, correspondingly. The values of sensitivity and specificity were around 90% in all series; also the false alarm rate values were under 10.5% for all sets. In addition, a simulated ligand-based virtual screening for several compounds recently reported as promising anti-chagasic agents was carried out, yielding good agreement between predictions and experimental results. Finally, the present work constitutes an example of how this rational computer-based method can help reduce the cost and increase the rate in which novel compounds are developed against Chagas disease.
Filiaciones:
Castillo-Garit, J:
Univ Ciencias Med Villa Clara, Unidad Toxicol Expt, Villa Clara, Cuba
Univ Valencia, Fac Farm, Dept Quim Fis, Unidad Invest Diseno Farm & Conectividad Mol, Valencia, Spain
Barigye, S:
Univ Autonoma Madrid UAM, Fac Ciencias, Dept Quim Fis Aplicada, Madrid, Spain
Pham-the, H:
Hanoi Univ Pharm, Dept Pharmaceut Chem, Hanoi, Vietnam
:
Hosp Univ Ribera, Dept Microbiol, Valencia, Spain
Torrens, F:
Univ Valencia, Inst Univ Ciencia Mol, Edifici Inst Paterna, Valencia, Spain
Perez-Gimenez, F:
Univ Valencia, Fac Farm, Dept Quim Fis, Unidad Invest Diseno Farm & Conectividad Mol, Valencia, Spain
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