| Author | Neves, Bruno Junior | |
| Author | Dantas, Rafael Ferreira | |
| Author | Senger, Mario Roberto | |
| Author | Valente, Walter César Góes | |
| Author | Rezende Neto, João de Mello | |
| Author | Chaves, William Távora | |
| Author | Kamentsky, Lee | |
| Author | Carpenter, Anne | |
| Author | Silva Junior, Floriano Paes | |
| Author | Andrade, Carolina Horta | |
| Access date | 2016-07-05T17:13:15Z | pt_BR |
| Access date | 2016-07-08T12:22:02Z | |
| Available date | 2016-07-05T17:13:15Z | pt_BR |
| Available date | 2016-07-08T12:22:02Z | |
| Document date | 2016 | |
| Citation | NEVES, Bruno Junior; etal. The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery. MedChemComm, v.7, p.1176-1182, Apr. 2016. | pt_BR |
| ISSN | 2040-2503 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/14784 | |
| Language | eng | pt_BR |
| Publisher | Royal Society of Chemistry | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Esquistossomose | pt_BR |
| Subject in Portuguese | Medicamento antidepressivo | pt_BR |
| Subject in Portuguese | Paroxetina | pt_BR |
| Title | The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery | pt_BR |
| Type | Article | |
| DOI | 10.1039/c5md00596e | pt_BR |
| Abstract | Recently, our in silico repositioning-chemogenomics approach predicted paroxetine (PAR), an antidepressant
drug, as a inhibitor of Schistosoma mansoni serotonin transporters (SmSERTs), and consequently, a
new anti-schistosomal candidate. With the aim of determining the anti-schistosomal activity of this drug, we
initially used a spectrophotometric assay to determine activity against schistosomula worms. During this investigation,
we verified that PAR showed a pronounced effect on schistosomula viability (IC50 = 2.5 μM) after
72 h of incubation. Then, we performed ex vivo studies with adult S. mansoni worms using a new automated
image-based assay to accurately measure worm motility. As expected from the PAR's predicted
mechanism of action, both male and female worms treated with low concentrations of PAR exhibited enhanced
motility followed by reduction in motility as incubation time increased. PAR EC50 values for motility
reduction in male and female worms were 5.1 μM and 9.9 μM after 24 h of exposure, respectively, and this
effect was maintained until the end of the experiment (72 h). Lastly, homology modeling and docking studies
with SmSERT-A and human SERT (hSERT) revealed insights into the chemical basis of PAR antischistosomal
activity. These results provide crucial guidance for further studies to optimize PAR in terms of
potency and selectivity. | pt_BR |
| Affilliation | Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design. Goiânia, GO, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Broad Institute of Massachusetts Institute of Technology and Harvard. Imaging Platform. Cambridge, Massachussetts, USA. | pt_BR |
| Affilliation | Broad Institute of Massachusetts Institute of Technology and Harvard. Imaging Platform. Cambridge, Massachussetts, USA | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design. Goiânia, GO, Brasil. | pt_BR |
| Subject | schistosome | pt_BR |
| Subject | Antidepressant drug | pt_BR |
| Subject | Paroxetine (PAR) | pt_BR |
| e-ISSN | 2040-2511 | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
