Computational Drug Repositioning for Chagas Disease Using Protein-Ligand Interaction Profiling

Simple item page
AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:33:34Z
Fecha de publicación2020-01-01
ResumenChagas disease, caused byTrypanosoma cruzi(T. cruzi), affects nearly eight million people worldwide. There are currently only limited treatment options, which cause several side effects and have drug resistance. Thus, there is a great need for a novel, improved Chagas treatment. Bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) has emerged as a promising pharmacological target. Moreover, some human dihydrofolate reductase (HsDHFR) inhibitors such as trimetrexate also inhibitT. cruziDHFR-TS (TcDHFR-TS). These compounds serve as a starting point and a reference in a screening campaign to search for newTcDHFR-TS inhibitors. In this paper, a novel virtual screening approach was developed that combines classical docking with protein-ligand interaction profiling to identify drug repositioning opportunities againstT. cruziinfection. In this approach, some food and drug administration (FDA)-approved drugs that were predicted to bind with high affinity toTcDHFR-TS and whose predicted molecular interactions are conserved among known inhibitors were selected. Overall, ten putativeTcDHFR-TS inhibitors were identified. These exhibited a similar interaction profile and a higher computed binding affinity, compared to trimetrexate. Nilotinib, glipizide, glyburide and gliquidone were tested onT. cruziepimastigotes and showed growth inhibitory activity in the micromolar range. Therefore, these compounds could lead to the development of new treatment options for Chagas disease.es_ES
Doihttps://doi.org/10.3390/ijms21124270es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/5399
Idiomaenes_ES
EditorialMDPIes_ES
RelaciónInternational Journal of Molecular Scienceses_ES
URL relacionadohttps://doi.org/10.3390/ijms21124270es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteInternational Journal of Molecular Sciences
Palabra claveantiprotozoales_ES
Palabra clavechagas diseasees_ES
Palabra claveFDA-Drugses_ES
Palabra clavemolecular dockinges_ES
Palabra claveprotein-ligand interaction profileres_ES
Palabra claverepositioninges_ES
TítuloComputational Drug Repositioning for Chagas Disease Using Protein-Ligand Interaction Profilinges_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorJuarez-Saldivar, Alfredo
AutorSchroeder, Michael
AutorSalentin, Sebastian
AutorHaupt, V. Joachim
AutorSaavedra, Emma
AutorVazquez, Citlali
AutorReyes-Espinosa, Francisco
AutorHerrera-Mayorga, Veronica
AutorVillalobos-Rocha, Juan Carlos
AutorGarcia-Perez, Carlos A.
AutorCampillo, Nuria E.
AutorRivera, Gildardo
AutorJuarez-Saldivar, Alfredoes_ES
AutorSchroeder, Michaeles_ES
AutorSalentin, Sebastianes_ES
AutorHaupt, V. Joachimes_ES
AutorSaavedra, Emmaes_ES
AutorVazquez, Citlalies_ES
AutorReyes-Espinosa, Franciscoes_ES
AutorHerrera-Mayorga, Veronicaes_ES
AutorVillalobos-Rocha, Juan Carloses_ES
AutorGarcia-Perez, Carlos A.es_ES
AutorCampillo, Nuria E.es_ES
AutorRivera, Gildardoes_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número12es_ES
URL relacionadahttps://doi.org/10.3390/ijms21124270
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen21es_ES

Files

Collections

Documentación Cientifica