title: Designing novel antitrypanosomal agents from a mixed graph-theoretical substructural approach.
abstract: Chagas disease is nowadays the most serious parasitic health problem. This disease is caused by Trypanosoma cruzi. The great number of deaths and the insufficient effectiveness of drugs against this parasite have alarmed the scientific community worldwide. In an attempt to overcome this problem, a model for the design and prediction of new antitrypanosomal agents was obtained. This used a mixed approach, containing simple descriptors based on fragments and topological substructural molecular design descriptors. A data set was made up of 188 compounds, 99 of them characterized an antitrypanosomal activity and 88 compounds that belong to other pharmaceutical categories. The model showed sensitivity, specificity and accuracy values above 85%. Quantitative fragmental contributions were also calculated. Then, and to confirm the quality of the model, 15 structures of molecules tested as antitrypanosomal compounds (that we did not include in this study) were predicted, taking into account the information on the abovementioned calculated fragmental contributions. The model showed an accuracy of 100% which means that the "in silico" methodology developed by our team is promising for the rational design of new antitrypanosomal drugs.
authors.affiliation: Department of Chemistry, Faculty of Natural Sciences, University of Oriente, Santiago de Cuba 90500, Cuba. alejspivanovich@yahoo.es
authors.forename: Alejandro Speck
authors.initials: AS
authors.lastname: Planche
authors.forename: Marcus Tulius
authors.initials: MT
authors.lastname: Scotti
authors.forename: Vicente de Paulo
authors.initials: Vde P
authors.lastname: Emerenciano
authors.forename: América García
authors.initials: AG
authors.lastname: López
authors.forename: Enrique Molina
authors.initials: EM
authors.lastname: Pérez
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D003198:Computer Simulation; D016002:Discriminant Analysis; D015195:Drug Design; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D014344:Trypanocidal Agents