Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Quantitative Structure-Activity Relationships for Structurally Diverse Chemotypes Having Anti-Trypanosoma cruzi Activity

Texto completo
Autor(es):
de Souza, Anacleto S. [1] ; Ferreira, Leonardo L. G. [1] ; de Oliveira, Aldo S. [1, 2] ; Andricopulo, Adriano D. [1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Fed Santa Catarina, Blumenal Ctr, Dept Exact Sci & Educ, BR-89036256 Blumenau - Brazil
[2] Univ Sao Paulo, Phys Inst Sao Carlos, Ctr Res & Innovat Biodivers & Drug Discovery, Lab Computat & Med Chem, BR-13563120 Sao Carlos, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 11 JUN 1 2019.
Citações Web of Science: 0
Resumo

Small-molecule compounds that have promising activity against macromolecular targets from Trypanosoma cruzi occasionally fail when tested in whole-cell phenotypic assays. This outcome can be attributed to many factors, including inadequate physicochemical and pharmacokinetic properties. Unsuitable physicochemical profiles usually result in molecules with a poor ability to cross cell membranes. Quantitative structure-activity relationship (QSAR) analysis is a valuable approach to the investigation of how physicochemical characteristics affect biological activity. In this study, artificial neural networks (ANNs) and kernel-based partial least squares regression (KPLS) were developed using anti-T. cruzi activity data for broadly diverse chemotypes. The models exhibited a good predictive ability for the test set compounds, yielding q(2) values of 0.81 and 0.84 for the ANN and KPLS models, respectively. The results of this investigation highlighted privileged molecular scaffolds and the optimum physicochemical space associated with high anti-T. cruzi activity, which provided important guidelines for the design of novel trypanocidal agents having drug-like properties. (AU)

Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
Beneficiário:Glaucius Oliva
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs