In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2012 |
| 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/15959 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. |
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Silva, Cristiane França daBatista, Denise da Gama JaenOliveira, Gabriel MeloSouza, Elen Mello deHammer, Erica RipollSilva, Patricia Bernardino daDaliry, AnissaAraujo, Julianna SicilianoBritto, ConstançaRodrigues, Ana Carolina MondaineLiu, ZongyingFarahat, Abdelbasset A.Kumar, ArvindBoykin, David W.Soeiro, Maria de Nazaré Correia2016-09-27T13:26:45Z2016-09-27T13:26:45Z2012SILVA, Cristiane França da; et al. In Vitro and In Vivo Investigation of the Efficacy of Arylimidamide DB1831 and Its Mesylated Salt Form - DB1965 - against Trypanosoma cruzi Infection. PLoS One, v.7, n.1, e30356, 8p, Jan. 2012.1932-6203https://www.arca.fiocruz.br/handle/icict/1595910.1371/journal.pone.0030356engPublic Library of ScienceTrypanosoma cruziDoença de ChagasArylimidamidesTratamentoTrypanosoma cruziChagas DiseasearyimidamidesTherapeuticIn vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Chagas disease is caused by infection with the intracellular protozoan parasite Trypanosoma cruzi. At present, nifurtimox and benznidazole, both compounds developed empirically over four decades ago, represent the chemotherapeutic arsenal for treating this highly neglected disease. However, both drugs present variable efficacy depending on the geographical area and the occurrence of natural resistance, and are poorly effective against the later chronic stage. As a part of a search for new therapeutic opportunities to treat chagasic patients, pre-clinical studies were performed to characterize the activity of a novel arylimidamide (AIA--DB1831 (hydrochloride salt) and DB1965 (mesylate salt)) against T. cruzi. These AIAs displayed a high trypanocidal effect in vitro against both relevant forms in mammalian hosts, exhibiting a high selectivity index and a very high efficacy (IC(50) value/48 h of 5-40 nM) against intracellular parasites. DB1965 shows high activity in vivo in acute experimental models (mouse) of T. cruzi, showing a similar effect to benznidazole (Bz) when compared under a scheme of 10 daily consecutive doses with 12.5 mg/kg. Although no parasitological cure was observed after treating with 20 daily consecutive doses, a combined dosage of DB1965 (5 mg/kg) with Bz (50 mg/kg) resulted in parasitaemia clearance and 100% animal survival. In summary, our present data confirmed that aryimidamides represent promising new chemical entities against T. cruzi in therapeutic schemes using the AIA alone or in combination with other drugs, like benznidazole.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/15959/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALdenise_batista_etal_IOC_2012.pdfdenise_batista_etal_IOC_2012.pdfapplication/pdf222191https://www.arca.fiocruz.br/bitstream/icict/15959/2/denise_batista_etal_IOC_2012.pdfb9870e72d1f2eea70bd960d321af8246MD52TEXTdenise_batista_etal_IOC_2012.pdf.txtdenise_batista_etal_IOC_2012.pdf.txtExtracted texttext/plain43537https://www.arca.fiocruz.br/bitstream/icict/15959/3/denise_batista_etal_IOC_2012.pdf.txt6f2298f874fab1782aa640f6758e1390MD53icict/159592018-04-02 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| dc.title.pt_BR.fl_str_mv |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| title |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| spellingShingle |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection Silva, Cristiane França da Trypanosoma cruzi Doença de Chagas Arylimidamides Tratamento Trypanosoma cruzi Chagas Disease aryimidamides Therapeutic |
| title_short |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| title_full |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| title_fullStr |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| title_full_unstemmed |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| title_sort |
In vitro and in vivo investigation of the efficacy of arylimidamide DB1831 and its mesylated salt form--DB1965--against Trypanosoma cruzi infection |
| author |
Silva, Cristiane França da |
| author_facet |
Silva, Cristiane França da Batista, Denise da Gama Jaen Oliveira, Gabriel Melo Souza, Elen Mello de Hammer, Erica Ripoll Silva, Patricia Bernardino da Daliry, Anissa Araujo, Julianna Siciliano Britto, Constança Rodrigues, Ana Carolina Mondaine Liu, Zongying Farahat, Abdelbasset A. Kumar, Arvind Boykin, David W. Soeiro, Maria de Nazaré Correia |
| author_role |
author |
| author2 |
Batista, Denise da Gama Jaen Oliveira, Gabriel Melo Souza, Elen Mello de Hammer, Erica Ripoll Silva, Patricia Bernardino da Daliry, Anissa Araujo, Julianna Siciliano Britto, Constança Rodrigues, Ana Carolina Mondaine Liu, Zongying Farahat, Abdelbasset A. Kumar, Arvind Boykin, David W. Soeiro, Maria de Nazaré Correia |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Silva, Cristiane França da Batista, Denise da Gama Jaen Oliveira, Gabriel Melo Souza, Elen Mello de Hammer, Erica Ripoll Silva, Patricia Bernardino da Daliry, Anissa Araujo, Julianna Siciliano Britto, Constança Rodrigues, Ana Carolina Mondaine Liu, Zongying Farahat, Abdelbasset A. Kumar, Arvind Boykin, David W. Soeiro, Maria de Nazaré Correia |
| dc.subject.other.pt_BR.fl_str_mv |
Trypanosoma cruzi Doença de Chagas Arylimidamides Tratamento |
| topic |
Trypanosoma cruzi Doença de Chagas Arylimidamides Tratamento Trypanosoma cruzi Chagas Disease aryimidamides Therapeutic |
| dc.subject.en.pt_BR.fl_str_mv |
Trypanosoma cruzi Chagas Disease aryimidamides Therapeutic |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. |
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2012 |
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2012 |
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2016-09-27T13:26:45Z |
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2016-09-27T13:26:45Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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SILVA, Cristiane França da; et al. In Vitro and In Vivo Investigation of the Efficacy of Arylimidamide DB1831 and Its Mesylated Salt Form - DB1965 - against Trypanosoma cruzi Infection. PLoS One, v.7, n.1, e30356, 8p, Jan. 2012. |
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https://www.arca.fiocruz.br/handle/icict/15959 |
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1932-6203 |
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10.1371/journal.pone.0030356 |
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SILVA, Cristiane França da; et al. In Vitro and In Vivo Investigation of the Efficacy of Arylimidamide DB1831 and Its Mesylated Salt Form - DB1965 - against Trypanosoma cruzi Infection. PLoS One, v.7, n.1, e30356, 8p, Jan. 2012. 1932-6203 10.1371/journal.pone.0030356 |
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