title: Identification in silico and in vitro of novel trypanosomicidal drug-like compounds.
abstract: Atom-based bilinear indices and linear discriminant analysis are used to discover novel trypanosomicidal compounds. The obtained linear discriminant analysis-based quantitative structure-activity relationship models, using non-stochastic and stochastic indices, provide accuracies of 89.02% (85.11%) and 89.60% (88.30%) of the chemicals in the training (test) sets, respectively. Later, both models were applied to the virtual screening of 18 in-house synthesized compounds to find new pro-lead antitrypanosomal agents. The in vitro antitrypanosomal activity of this set against epimastigote forms of Trypanosoma cruzi is assayed. Predictions agree with experimental results to a great extent (16/18) of the chemicals. Sixteen compounds show more than 70% of epimastigote inhibition at a concentration 100 μg/mL. In addition, three compounds (CRIS 112, CRIS 140 and CRIS 147) present more than 70% of epimastigote inhibition at a concentration of 10 μg/mL (79.95%, 73.97% and 78.13%, respectively) with low values of cytotoxicity (19.7%, 7.44% and 20.63%, correspondingly).Taking into account all these results, we could say that these three compounds could be optimized in forthcoming works. Even though none of them resulted more active than nifurtimox, the current results constitute a step forward in the search for efficient ways to discover new lead antitrypanosomals.
authors.affiliation: Applied Chemistry Research Center, Faculty of Chemistry-Pharmacy, Universidad Central "Marta Abreu" de Las Villas, Santa Clara, 54830 Villa Clara, Cuba. jacgarit@yahoo.es
authors.forename: Juan A
authors.initials: JA
authors.lastname: Castillo-Garit
authors.forename: Oremia
authors.initials: O
authors.lastname: Del Toro-Cortés
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Kouznetsov
authors.forename: Cristian Ochoa
authors.initials: CO
authors.lastname: Puentes
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Romero Bohórquez
authors.forename: Maria C
authors.initials: MC
authors.lastname: Vega
authors.forename: Miriam
authors.initials: M
authors.lastname: Rolón
authors.forename: José A
authors.initials: JA
authors.lastname: Escario
authors.forename: Alicia
authors.initials: A
authors.lastname: Gómez-Barrio
authors.forename: Yovani
authors.initials: Y
authors.lastname: Marrero-Ponce
authors.forename: Francisco
authors.initials: F
authors.lastname: Torrens
authors.forename: Concepción
authors.initials: C
authors.lastname: Abad
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016002:Discriminant Analysis; D051379:Mice; D021281:Quantitative Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D014344:Trypanocidal Agents