Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2014 |
| 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/9400 |
Resumo: | Pontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, Brazil/Instituto Militar de Engenharia. Laboratorio de Modelagem Aplicada a Defesa Quımica e Biologica. Rio de Janeiro, RJ, Brazil, |
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Cortopassi, Wilian A.Coutinho, Julia PennaAguiar, Anna Caroline CamposPimentel, Andre S.Buarque, Camilla D.Costa, Paulo Roberto RibeiroAlves, Bruna R. M.Franca, Tanos Celmar CostaKrettli, Antoniana Ursine2015-01-29T13:26:21Z2015-01-29T13:26:21Z2014CORTOPASSI, Wilian A, et al. Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum. PLoS ONE; v. 9. n. 3, p. e91191, 2014.1553-7366https://www.arca.fiocruz.br/handle/icict/940010.1371/journal.pone.0091191engPublic Library of ScienceTheoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparuminfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlePontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, Brazil/Instituto Militar de Engenharia. Laboratorio de Modelagem Aplicada a Defesa Quımica e Biologica. Rio de Janeiro, RJ, Brazil,Fundação Instituto Oswaldo Cruz. Laboratorio de Malaria, Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrazilFundação Instituto Oswaldo Cruz. Laboratorio de Malaria, Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrazilPontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, BrazilPontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, BrazilNucleo de Pesquisas de Produtos Naturais. Laboratorio de Quımica Bioorganica. Rio de Janeiro, RJ, BrazilPontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, BrazilInstituto Militar de Engenharia. Laboratorio de Modelagem Aplicada a Defesa Quımica e Biologica. Rio de Janeiro, RJ, BrazilFundação Instituto Oswaldo Cruz. Laboratorio de Malaria, Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina. Belo Horizonte, MG, BrazilDNA topoisomerase I from Plasmodium falciparum (PfTopoI), a potential selective target for chemotherapy and drug development against malaria, is used here, together with human Topo I (HssTopoI), for docking, molecular dynamics (MD) studies and experimental assays. Six synthetic isoflavonoid derivatives and the known PfTopoI inhibitors camptothecin and topotecan were evaluated in parallel. Theoretical results suggest that these compounds dock in the binding site of camptothecin and topotecan inside both enzymes and that LQB223 binds selectively in PfTopoI. In vitro tests against P. falciparum blood parasites corroborated the theoretical findings. The selectivity index (SI) of LQB223 $98 suggests that this molecule is the most promising in the group of compounds tested. In vivo experiments in mice infected with P. berghei showed that LQB223 has an antimalarial activity similar to that of chloroquine.AntimalarialsDrug therapyMalariaMalarial parasitesParasitemiaParasitic diseasesPlasmodiumProtein interactionsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/9400/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINAL2014_012.pdf2014_012.pdfapplication/pdf737217https://www.arca.fiocruz.br/bitstream/icict/9400/2/2014_012.pdfd93c15227f510c4d1161c7d85d265c28MD52TEXT2014_012.pdf.txt2014_012.pdf.txtExtracted texttext/plain33561https://www.arca.fiocruz.br/bitstream/icict/9400/3/2014_012.pdf.txtbb45572ce2e75e733b8191960ae0176eMD53icict/94002019-06-19 10:07:32.584oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:07:32Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| title |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| spellingShingle |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum Cortopassi, Wilian A. Antimalarials Drug therapy Malaria Malarial parasites Parasitemia Parasitic diseases Plasmodium Protein interactions |
| title_short |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| title_full |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| title_fullStr |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| title_full_unstemmed |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| title_sort |
Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum |
| author |
Cortopassi, Wilian A. |
| author_facet |
Cortopassi, Wilian A. Coutinho, Julia Penna Aguiar, Anna Caroline Campos Pimentel, Andre S. Buarque, Camilla D. Costa, Paulo Roberto Ribeiro Alves, Bruna R. M. Franca, Tanos Celmar Costa Krettli, Antoniana Ursine |
| author_role |
author |
| author2 |
Coutinho, Julia Penna Aguiar, Anna Caroline Campos Pimentel, Andre S. Buarque, Camilla D. Costa, Paulo Roberto Ribeiro Alves, Bruna R. M. Franca, Tanos Celmar Costa Krettli, Antoniana Ursine |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Cortopassi, Wilian A. Coutinho, Julia Penna Aguiar, Anna Caroline Campos Pimentel, Andre S. Buarque, Camilla D. Costa, Paulo Roberto Ribeiro Alves, Bruna R. M. Franca, Tanos Celmar Costa Krettli, Antoniana Ursine |
| dc.subject.en.pt_BR.fl_str_mv |
Antimalarials Drug therapy Malaria Malarial parasites Parasitemia Parasitic diseases Plasmodium Protein interactions |
| topic |
Antimalarials Drug therapy Malaria Malarial parasites Parasitemia Parasitic diseases Plasmodium Protein interactions |
| description |
Pontifıcia Universidade Catolica do Rio de Janeiro. Departamento de Quımica. Rio de Janeiro, RJ, Brazil/Instituto Militar de Engenharia. Laboratorio de Modelagem Aplicada a Defesa Quımica e Biologica. Rio de Janeiro, RJ, Brazil, |
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2014 |
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2014 |
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2015-01-29T13:26:21Z |
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2015-01-29T13:26:21Z |
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info:eu-repo/semantics/article |
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CORTOPASSI, Wilian A, et al. Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum. PLoS ONE; v. 9. n. 3, p. e91191, 2014. |
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https://www.arca.fiocruz.br/handle/icict/9400 |
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1553-7366 |
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10.1371/journal.pone.0091191 |
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CORTOPASSI, Wilian A, et al. Theoretical and Experimental Studies of New Modified Isoflavonoids as Potential Inhibitors of Topoisomerase I from Plasmodium falciparum. PLoS ONE; v. 9. n. 3, p. e91191, 2014. 1553-7366 10.1371/journal.pone.0091191 |
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