Mefloquine-oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: in vitro activity including against the multidrug-resistant tuberculosis strain T113

Detalhes bibliográficos
Autor(a) principal: Gonçalves, Raoni S. B.
Data de Publicação: 2012
Outros Autores: 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
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
id CRUZ_899c3331b27ff42a58e13ca1f628cb70
oai_identifier_str oai:www.arca.fiocruz.br:icict/36429
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling 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
dc.date.issued.fl_str_mv 2012
dc.date.accessioned.fl_str_mv 2019-10-15T12:00:54Z
dc.date.available.fl_str_mv 2019-10-15T12:00:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv 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.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/36429
dc.identifier.issn.pt_BR.fl_str_mv 0968-0896
dc.identifier.doi.none.fl_str_mv 10.1016/j.bmc.2011.11.006
identifier_str_mv 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
url https://www.arca.fiocruz.br/handle/icict/36429
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/36429/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/36429/2/ve_Gon%c3%a7alves_Raoni_etal_INI_2012.pdf
https://www.arca.fiocruz.br/bitstream/icict/36429/3/ve_Gon%c3%a7alves_Raoni_etal_INI_2012.pdf.txt
bitstream.checksum.fl_str_mv 8a4605be74aa9ea9d79846c1fba20a33
048a521ae3d52941dc4f626bcc4dfb98
8c74133a9a46bc9ca5be626f04bd58f2
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1813009290505486336