| Author | Neves, Bruno J. | |
| Author | Dantas, Rafael F. | |
| Author | Senger, Mario R. | |
| Author | Valente, Walter C. G. | |
| Author | Almeida, Ana C. M. de | |
| Author | Rezende Neto, João M. | |
| Author | Lima, Elid F. C. | |
| Author | Paveley, Ross | |
| Author | Furnham, Nicholas | |
| Author | Muratov, Eugene | |
| Author | Kamentsky, Lee | |
| Author | Carpenter, Anne E. | |
| Author | Braga, Rodolfo C. | |
| Author | Silva Junior, Floriano P. | |
| Author | Andrade, Carolina H. | |
| Access date | 2017-07-20T13:35:21Z | |
| Available date | 2017-07-20T13:35:21Z | |
| Document date | 2016 | |
| Citation | NEVES, Bruno J. et al. Discovery of New Anti-Schistosomal Hits by Integration of QSAR-Based Virtual Screening and High Content Screening. Journal of Medicinal Chemistry, v.59, n.15, p.7075-7088, Aug. 2016. | pt_BR |
| ISSN | 0022-2623 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/20156 | |
| Language | eng | pt_BR |
| Publisher | American Chemical Society | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Medicina molecular | pt_BR |
| Subject in Portuguese | Esquistossomose | pt_BR |
| Subject in Portuguese | Doenças Negligenciadas | pt_BR |
| Title | Discovery of New Anti-Schistosomal Hits by Integration of QSAR-Based Virtual Screening and High Content Screening | pt_BR |
| Type | Article | |
| Abstract | Schistosomiasis is a debilitating neglected tropical disease, caused by flatworms of Schistosoma genus. The treatment relies on a single drug, praziquantel (PZQ), making the discovery of new compounds extremely urgent. In this work, we integrated QSAR-based virtual screening (VS) of Schistosoma mansoni thioredoxin glutathione reductase (SmTGR) inhibitors and high content screening (HCS) aiming to discover new antischistosomal agents. Initially, binary QSAR models for inhibition of SmTGR were developed and validated using the Organization for Economic Co-operation and Development (OECD) guidance. Using these models, we prioritized 29 compounds for further testing in two HCS platforms based on image analysis of assay plates. Among them, 2-[2-(3-methyl-4-nitro-5-isoxazolyl)vinyl]pyridine and 2-(benzylsulfonyl)-1,3-benzothiazole, two compounds representing new chemical scaffolds have activity against schistosomula and adult worms at low micromolar concentrations and therefore represent promising antischistosomal hits for further hit-to-lead optimization. | pt_BR |
| Affilliation | Universidade Federal de Goias. Faculdade de Farmácia. Laboratório de Planejamento de Fármacos e Modelagem Molecular. 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 | Universidade Federal de Goias. Faculdade de Farmácia. Laboratório de Planejamento de Fármacos e Modelagem Molecular. 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 | London School of Hygiene and Tropical Medicine. Department of Infection and Immunity. London, United Kingdom. | pt_BR |
| Affilliation | London School of Hygiene and Tropical Medicine. Department of Infection and Immunity. London, United Kingdom. | pt_BR |
| Affilliation | University of North Carolina. Eshelman School of Pharmacy. Laboratory for Molecular Modeling. Chapel Hill, NC, USA. | pt_BR |
| Affilliation | Broad Institute of Massachusetts Institute of Technology and Harvard. Imaging Platform.Cambridge, Massachusetts, USA.. | pt_BR |
| Affilliation | Broad Institute of Massachussetts Institute of Technology and Harvard. Imaging Platform. Cambridge, Massachussetts, USA. | pt_BR |
| Affilliation | Universidade Federal de Goias. Faculdade de Farmácia. Laboratório de Planejamento de Fármacos e Modelagem Molecular. Goiânia, GO, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Goias. Faculdade de Farmácia. Laboratório de Planejamento de Fármacos e Modelagem Molecular. Goiânia, GO, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Goias. Faculdade de Farmácia. Laboratório de Planejamento de Fármacos e Modelagem Molecular. Goiânia, GO, Brasil. | pt_BR |
| Subject | Schistosoma mansoni | pt_BR |
| Subject | Schistosomiasis | pt_BR |
| Subject | Neglected Diseases | pt_BR |
| Subject | Molecular Medicine | pt_BR |
| Subject | Neglected Diseases | pt_BR |
| e-ISSN | 1520-4804 | |
| Embargo date | 2030-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
