Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113
| 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/36429 |
Resumo: | 2020-10-15 |
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Gonçalves, Raoni S. B.Kaiser, Carlos R.Lourenço, Maria C. S.Bezerra, Flavio A. F. M.Souza, Marcus V. N. deWardell, James L.Wardell, Solange M. S. V.Henriques, Maria das Graças M. de O.Costa, Thadeu2019-10-15T12:00:54Z2019-10-15T12:00:54Z2012GONÇALVES, Raoni S. B. et al. Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113. Bioorganic & Medicinal Chemistry, v. 20, p. 243-248, 2012.0968-0896https://www.arca.fiocruz.br/handle/icict/3642910.1016/j.bmc.2011.11.006engElsevierMefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2020-10-15Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Química. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Química. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Química. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Desenvolvimento Tecnológico em Saúde. Rio de Janeiro, RJ, Brasil.CHEMSOL. Aberdeen, Scotland, UK.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brasil.Ten new mefloquine–oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl = substituted phenyl) and 4-[(1S,8aR)-3-(heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline [2: heteroaryl = 5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl = 3-ethoxyphenyl), 1g (Ar = 3,4,5-(MeO)3-C6H2) and 2c were slightly more active than mefloquine (MIC = 33 μM) with MICs = 24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl = 3,4-(MeO)2-C6H3) and 2a (MICs = 11.9 and 12.1 μM, respectively) were ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity than the first line tuberculostatic agent ethambutol (MIC = 15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values.Multidrug-resistant tuberculosisQuinolineMefloquineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/36429/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALve_Gonçalves_Raoni_etal_INI_2012.pdfve_Gonçalves_Raoni_etal_INI_2012.pdfapplication/pdf360358https://www.arca.fiocruz.br/bitstream/icict/36429/2/ve_Gon%c3%a7alves_Raoni_etal_INI_2012.pdf048a521ae3d52941dc4f626bcc4dfb98MD52TEXTve_Gonçalves_Raoni_etal_INI_2012.pdf.txtve_Gonçalves_Raoni_etal_INI_2012.pdf.txtExtracted texttext/plain34652https://www.arca.fiocruz.br/bitstream/icict/36429/3/ve_Gon%c3%a7alves_Raoni_etal_INI_2012.pdf.txt8c74133a9a46bc9ca5be626f04bd58f2MD53icict/364292021-03-24 16:32:37.493oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352021-03-24T19:32:37Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| title |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| spellingShingle |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 Gonçalves, Raoni S. B. Multidrug-resistant tuberculosis Quinoline Mefloquine |
| title_short |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| title_full |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| title_fullStr |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| title_full_unstemmed |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| title_sort |
Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113 |
| author |
Gonçalves, Raoni S. B. |
| author_facet |
Gonçalves, Raoni S. B. Kaiser, Carlos R. Lourenço, Maria C. S. Bezerra, Flavio A. F. M. Souza, Marcus V. N. de Wardell, James L. Wardell, Solange M. S. V. Henriques, Maria das Graças M. de O. Costa, Thadeu |
| author_role |
author |
| author2 |
Kaiser, Carlos R. Lourenço, Maria C. S. Bezerra, Flavio A. F. M. Souza, Marcus V. N. de Wardell, James L. Wardell, Solange M. S. V. Henriques, Maria das Graças M. de O. Costa, Thadeu |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Gonçalves, Raoni S. B. Kaiser, Carlos R. Lourenço, Maria C. S. Bezerra, Flavio A. F. M. Souza, Marcus V. N. de Wardell, James L. Wardell, Solange M. S. V. Henriques, Maria das Graças M. de O. Costa, Thadeu |
| dc.subject.en.pt_BR.fl_str_mv |
Multidrug-resistant tuberculosis Quinoline Mefloquine |
| topic |
Multidrug-resistant tuberculosis Quinoline Mefloquine |
| description |
2020-10-15 |
| publishDate |
2012 |
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2012 |
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2019-10-15T12:00:54Z |
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2019-10-15T12:00:54Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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GONÇALVES, Raoni S. B. et al. Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113. Bioorganic & Medicinal Chemistry, v. 20, p. 243-248, 2012. |
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https://www.arca.fiocruz.br/handle/icict/36429 |
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0968-0896 |
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10.1016/j.bmc.2011.11.006 |
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GONÇALVES, Raoni S. B. et al. Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113. Bioorganic & Medicinal Chemistry, v. 20, p. 243-248, 2012. 0968-0896 10.1016/j.bmc.2011.11.006 |
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Elsevier |
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Elsevier |
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