Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-09-15T00:30:13Z
Fecha de publicación2017-01-01
ResumenChagas disease (CD) is a neglected disease caused by the parasite Trypanosoma cruzi, which affects underdeveloped countries. The current drugs of choice are nifurtimox and benznidazole, but both have severe adverse effects and less effectivity in chronic infections; therefore, the need to discover new drugs is essential. A computer-guided drug repositioning method was applied to identify potential FDA drugs (approved and withdrawn) as cruzain (Cz) inhibitors and trypanocidal effects were confirmed by in vitro and in vivo studies. 3180 FDA drugs were virtually screened using a structure-based approach. From a first molecular docking analysis, a set of 33 compounds with the best binding energies were selected. Subsequent consensus affinity binding, ligand amino acid contact clustering analysis, and ranked position were used to choose four known pharmacological compounds to be tested in vitro. Mouse blood samples infected with trypomastigotes from INC-5 and NINOA strains were used to test the trypanocidal effect of four selected compounds. Among these drugs, one fibrate antilipemic (etofyllin clofibrate) and three β-lactam antibiotics (piperacillin, cefoperazone, and flucloxacillin) showed better trypanocidal effects (LC50 range 15.8–26.1 μg/mL) in comparison with benznidazole and nifurtimox (LC50 range 33.1–46.7 μg/mL). A short-term in vivo evaluation of these compounds showed a reduction of parasitemia in infected mice (range 90–60%) at 6 h, but this was low compared to benznidazole (50%). This work suggests that four known FDA drugs could be used to design and obtain new trypanocidal agents.es_ES
Doihttps://doi.org/10.3390/molecules22061015es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/2166
Idiomaeses_ES
EditorialMDPI AGes_ES
RelaciónMoleculeses_ES
URL relacionadohttps://doi.org/10.3390/molecules22061015es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteMolecules
TítuloRepositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studieses_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
AutorPalos, Isidro
AutorLara-Ramirez, Edgar E.
AutorLopez-Cedillo, Julio Cesar
AutorGarcia-Perez, Carlos
AutorKashif, Muhammad
AutorBocanegra-Garcia, Virgilio
AutorNogueda-Torres, Benjamin
AutorRivera, Gildardo
AutorPalos, Isidroes_ES
AutorLara-Ramirez, Edgar E.es_ES
AutorLopez-Cedillo, Julio Cesares_ES
AutorGarcia-Perez, Carloses_ES
AutorKashif, Muhammades_ES
AutorBocanegra-Garcia, Virgilioes_ES
AutorNogueda-Torres, Benjamines_ES
AutorRivera, Gildardoes_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número6es_ES
Rango de páginas1015es_ES
URL relacionadahttps://doi.org/10.3390/molecules22061015
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen22es_ES

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