The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/14784 |
Resumo: | Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design. Goiânia, GO, Brasil. |
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Neves, Bruno JuniorDantas, Rafael FerreiraSenger, Mario RobertoValente, Walter César GóesRezende Neto, João de MelloChaves, William TávoraKamentsky, LeeCarpenter, AnneSilva Junior, Floriano PaesAndrade, Carolina Horta2016-07-05T17:13:15Z2016-07-08T12:22:02Z2016-07-05T17:13:15Z2016-07-08T12:22:02Z2016NEVES, Bruno Junior; etal. The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery. MedChemComm, v.7, p.1176-1182, Apr. 2016.2040-2503https://www.arca.fiocruz.br/handle/icict/1478410.1039/c5md00596e2040-2511engRoyal Society of ChemistryEsquistossomoseMedicamento antidepressivoParoxetinaschistosomeAntidepressant drugParoxetine (PAR)The antidepressant drug paroxetine as a new lead candidate in schistosome drug discoveryinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design. Goiânia, GO, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Broad Institute of Massachusetts Institute of Technology and Harvard. Imaging Platform. Cambridge, Massachussetts, USA.Broad Institute of Massachusetts Institute of Technology and Harvard. Imaging Platform. Cambridge, Massachussetts, USAFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design. Goiânia, GO, Brasil.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZTEXTwalter_valente_etal_IOC_2016.pdf.txtwalter_valente_etal_IOC_2016.pdf.txtExtracted texttext/plain33924https://www.arca.fiocruz.br/bitstream/icict/14784/4/walter_valente_etal_IOC_2016.pdf.txtd0068750e5630bac6431fece654196daMD54ORIGINALwalter_valente_etal_IOC_2016.pdfapplication/pdf3152264https://www.arca.fiocruz.br/bitstream/icict/14784/2/walter_valente_etal_IOC_2016.pdf5f57b17c051e5ab5c408b304050e98d6MD52LICENSElicense.txttext/plain2991https://www.arca.fiocruz.br/bitstream/icict/14784/3/license.txt5a560609d32a3863062d77ff32785d58MD53icict/147842022-06-24 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| dc.title.pt_BR.fl_str_mv |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| title |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| spellingShingle |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery Neves, Bruno Junior Esquistossomose Medicamento antidepressivo Paroxetina schistosome Antidepressant drug Paroxetine (PAR) |
| title_short |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| title_full |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| title_fullStr |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| title_full_unstemmed |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| title_sort |
The antidepressant drug paroxetine as a new lead candidate in schistosome drug discovery |
| author |
Neves, Bruno Junior |
| author_facet |
Neves, Bruno Junior Dantas, Rafael Ferreira Senger, Mario Roberto Valente, Walter César Góes Rezende Neto, João de Mello Chaves, William Távora Kamentsky, Lee Carpenter, Anne Silva Junior, Floriano Paes Andrade, Carolina Horta |
| author_role |
author |
| author2 |
Dantas, Rafael Ferreira Senger, Mario Roberto Valente, Walter César Góes Rezende Neto, João de Mello Chaves, William Távora Kamentsky, Lee Carpenter, Anne Silva Junior, Floriano Paes Andrade, Carolina Horta |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Neves, Bruno Junior Dantas, Rafael Ferreira Senger, Mario Roberto Valente, Walter César Góes Rezende Neto, João de Mello Chaves, William Távora Kamentsky, Lee Carpenter, Anne Silva Junior, Floriano Paes Andrade, Carolina Horta |
| dc.subject.other.pt_BR.fl_str_mv |
Esquistossomose Medicamento antidepressivo Paroxetina |
| topic |
Esquistossomose Medicamento antidepressivo Paroxetina schistosome Antidepressant drug Paroxetine (PAR) |
| dc.subject.en.pt_BR.fl_str_mv |
schistosome Antidepressant drug Paroxetine (PAR) |
| description |
Universidade Federal de Goiás. Faculdade de Farmácia. Laboratório de Modelagem Molecular e Design. Goiânia, GO, Brasil. |
| publishDate |
2016 |
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2016-07-05T17:13:15Z 2016-07-08T12:22:02Z |
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2016-07-05T17:13:15Z 2016-07-08T12:22:02Z |
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2016 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/14784 |
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2040-2503 |
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10.1039/c5md00596e |
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2040-2511 |
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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. 2040-2503 10.1039/c5md00596e 2040-2511 |
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Royal Society of Chemistry |
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Royal Society of Chemistry |
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