| Author | Sijm, Maarten | |
| Author | Araújo, Julianna Siciliano de | |
| Author | Ramos Llorca, Alba | |
| Author | Orrling, Kristina | |
| Author | Stiny, Lydia | |
| Author | Matheeussen, An | |
| Author | Maes, Louis | |
| Author | de Esch, Iwan J. P. | |
| Author | Soeiro, Maria de Nazaré C. | |
| Author | Sterk, Geert Jan | |
| Author | Leurs, Rob | |
| Access date | 2020-03-23T20:15:50Z | |
| Available date | 2020-03-23T20:15:50Z | |
| Document date | 2019 | |
| Citation | SJIM, Maarten et al. Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents. ChemMedChem, v. 14, p. 1662-1668, 2019. | pt_BR |
| ISSN | 1860-7179 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/40466 | |
| Language | eng | pt_BR |
| Publisher | Wiley | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Dímeros de fenilpirazolona | pt_BR |
| Subject in Portuguese | Identificação | pt_BR |
| Subject in Portuguese | Agentes anti-Trypanosoma cruzi | pt_BR |
| Title | Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents | pt_BR |
| Type | Article | |
| DOI | 10.1002/cmdc.201900370 | |
| Abstract | Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2'-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2'-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | Universiteit Antwerpen. Laboratory for Microbiology, Parasitology and Hygiene. Antwerp, Belgium. | pt_BR |
| Affilliation | Universiteit Antwerpen. Laboratory for Microbiology, Parasitology and Hygiene. Antwerp, Belgium. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Affilliation | Vrije Universiteit Amsterdam. Amsterdam Institute for Molecules, Medicines & Systems. Division of Medicinal Chemistry. Faculty of Science. Amsterdam, The Netherlands. | pt_BR |
| Subject | Phenylpyrazolone Dimers | pt_BR |
| Subject | Identification | pt_BR |
| Subject | Anti-Trypanosoma cruzi Agents | pt_BR |
| Subject | New Class | pt_BR |
| e-ISSN | 1860-7187 | |
| Embargo date | 2025-01-01 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
