Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening
Nowadays, the pharmacological therapy for the treatment of Chagas disease is based on two old drugs, benznidazole and nifurtimox, which have restricted efficacy against the chronic phase of the illness. To overcome the lack of efficacy of the traditional drugs (and their considerable toxicity), new...
| Autores principales: | , , , , , , |
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| Formato: | Articulo Preprint |
| Lenguaje: | Inglés |
| Publicado: |
2018
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/101758 https://ri.conicet.gov.ar/11336/94472 |
| Aporte de: |
| id |
I19-R120-10915-101758 |
|---|---|
| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Química Chagas disease Cisapride Docking Drug repositioning QSAR TcPAT12 TcPOT1.1. |
| spellingShingle |
Química Chagas disease Cisapride Docking Drug repositioning QSAR TcPAT12 TcPOT1.1. Dietrich, Roque Carlos Alberca, Lucas Nicolás Ruiz, María Daniela Palestro, Pablo Hernán Carrillo, Carolina Talevi, Alan Gavernet, Luciana Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| topic_facet |
Química Chagas disease Cisapride Docking Drug repositioning QSAR TcPAT12 TcPOT1.1. |
| description |
Nowadays, the pharmacological therapy for the treatment of Chagas disease is based on two old drugs, benznidazole and nifurtimox, which have restricted efficacy against the chronic phase of the illness. To overcome the lack of efficacy of the traditional drugs (and their considerable toxicity), new molecular targets have been studied as starting points to the discovery of new antichagasic compounds. Among them, polyamine transporter TcPAT12 (also known as TcPOT1.1) represents an interesting macromolecule, since polyamines are essential for Trypanosoma cruzi, the parasite that causes the illness, but it cannot synthesize them de novo. In this investigation we report the results of a combined ligand- and structure-based virtual screening for the discovery of new inhibitors of TcPAT12. Initially we filtered out ZINC and Drugbank databases with similarity and QSAR models and then we submitted the candidates to a validated docking based screening. Four structures were selected and tested in T. cruzi epimastigotes proliferation and two of them, Cisapride and [2-(cyclopentyloxy)phenyl]methanamine showed inhibitory effects. Additionally, we performed transport assays which demonstrated that Cisapride interferes with putrescine uptake in a specific mode. |
| format |
Articulo Preprint |
| author |
Dietrich, Roque Carlos Alberca, Lucas Nicolás Ruiz, María Daniela Palestro, Pablo Hernán Carrillo, Carolina Talevi, Alan Gavernet, Luciana |
| author_facet |
Dietrich, Roque Carlos Alberca, Lucas Nicolás Ruiz, María Daniela Palestro, Pablo Hernán Carrillo, Carolina Talevi, Alan Gavernet, Luciana |
| author_sort |
Dietrich, Roque Carlos |
| title |
Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| title_short |
Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| title_full |
Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| title_fullStr |
Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| title_full_unstemmed |
Identification of cisapride as new inhibitor of putrescine uptake in Trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| title_sort |
identification of cisapride as new inhibitor of putrescine uptake in trypanosoma cruzi by combined ligand- and structure-based virtual screening |
| publishDate |
2018 |
| url |
http://sedici.unlp.edu.ar/handle/10915/101758 https://ri.conicet.gov.ar/11336/94472 |
| work_keys_str_mv |
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Repositorios |
| _version_ |
1764820440223580160 |