Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells

Detalhes bibliográficos
Autor(a) principal: Calhelha, Ricardo C.
Data de Publicação: 2012
Outros Autores: Ferreira, Isabel C. F. R., Peixoto, Daniela, Abreu, Rui M. V., Silva, L. A. Vale, Pinto, Eugénia, Lima, Raquel T., Alvelos, Maria I., Vasconcelos, M. Helena, Queiroz, Maria João R. P.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/22006
Resumo: Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.
id RCAP_a2a2f7c9516ac8308b3ed5d8a1ec0d6c
oai_identifier_str oai:repositorium.sdum.uminho.pt:1822/22006
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cellsThieno[3,2-b]pyridinesAminodi(hetero)arylaminesBuchwald-hartwig C-N couplingAntitumoral activityToxicityCell cycleApoptosis2-b]pyridinesThieno[3Science & TechnologyThree aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.Foundation for the Science and Technology (FCT–Portugal) for financial support through the NMR Portuguese network (Bruker 400 Avance III-Univ Minho). FCT and FEDER (European Fund for Regional Development) for financial support through the research centers PEst-C/QUI/UI686/2011and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoralgrants attributed to R.C.C. and R.T.L. (SFRH/BPD/68344/2010 and SFRH/BPD/68787/2010, respectively). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT.MDPIUniversidade do MinhoCalhelha, Ricardo C.Ferreira, Isabel C. F. R.Peixoto, DanielaAbreu, Rui M. V.Silva, L. A. ValePinto, EugéniaLima, Raquel T.Alvelos, Maria I.Vasconcelos, M. HelenaQueiroz, Maria João R. P.2012-03-282012-03-28T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/22006eng1420-304910.3390/molecules1704383422456543www.mdpi.com/journal/moleculesinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:44:35Zoai:repositorium.sdum.uminho.pt:1822/22006Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:42:18.456785Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
title Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
spellingShingle Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
Calhelha, Ricardo C.
Thieno[3,2-b]pyridines
Aminodi(hetero)arylamines
Buchwald-hartwig C-N coupling
Antitumoral activity
Toxicity
Cell cycle
Apoptosis
2-b]pyridines
Thieno[3
Science & Technology
title_short Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
title_full Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
title_fullStr Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
title_full_unstemmed Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
title_sort Aminodi(hetero)arylamines in the thieno[3,2-b]pyridine series: synthesis, effects in human tumor cells growth, cell cycle analysis, apoptosis and evaluation of toxicity using non-tumor cells
author Calhelha, Ricardo C.
author_facet Calhelha, Ricardo C.
Ferreira, Isabel C. F. R.
Peixoto, Daniela
Abreu, Rui M. V.
Silva, L. A. Vale
Pinto, Eugénia
Lima, Raquel T.
Alvelos, Maria I.
Vasconcelos, M. Helena
Queiroz, Maria João R. P.
author_role author
author2 Ferreira, Isabel C. F. R.
Peixoto, Daniela
Abreu, Rui M. V.
Silva, L. A. Vale
Pinto, Eugénia
Lima, Raquel T.
Alvelos, Maria I.
Vasconcelos, M. Helena
Queiroz, Maria João R. P.
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Calhelha, Ricardo C.
Ferreira, Isabel C. F. R.
Peixoto, Daniela
Abreu, Rui M. V.
Silva, L. A. Vale
Pinto, Eugénia
Lima, Raquel T.
Alvelos, Maria I.
Vasconcelos, M. Helena
Queiroz, Maria João R. P.
dc.subject.por.fl_str_mv Thieno[3,2-b]pyridines
Aminodi(hetero)arylamines
Buchwald-hartwig C-N coupling
Antitumoral activity
Toxicity
Cell cycle
Apoptosis
2-b]pyridines
Thieno[3
Science & Technology
topic Thieno[3,2-b]pyridines
Aminodi(hetero)arylamines
Buchwald-hartwig C-N coupling
Antitumoral activity
Toxicity
Cell cycle
Apoptosis
2-b]pyridines
Thieno[3
Science & Technology
description Three aminodi(hetero)arylamines were prepared via a palladium-catalyzed C-N Buchwald-Hartwig coupling of methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with different bromonitrobenzenes, followed by reduction of the nitro groups of the coupling products to the corresponding amino compounds. The aminodi(hetero)arylamines thus obtained were evaluated for their growth inhibitory effect on four human tumor cell lines MCF-7 (breast adenocarcinoma), A375-C5 (melanoma), NCI-H460 (non-small cell lung cancer) and HepG2 (hepatocellular carcinoma). The toxicity to non-tumor cells was also evaluated using a porcine liver primary cell culture (PLP1), established by us. The aminodi(hetero)arylamine with the NH2 group in the ortho position and an OMe group in the para position to the NH of the di(hetero)arylamine, is the most promising compound giving the lowest GI50 values (1.30–1.63 μM) in all the tested human tumor cell lines, presenting no toxicity to PLP1 at those concentrations. The effect of this compound on the cell cycle and induction of apoptosis was analyzed in the NCI-H460 cell line. It was observed that it altered the cell cycle profile causing a decrease in the percentage of cells in the G0/G1 phase and an increase of the apoptosis levels.
publishDate 2012
dc.date.none.fl_str_mv 2012-03-28
2012-03-28T00:00:00Z
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.uri.fl_str_mv http://hdl.handle.net/1822/22006
url http://hdl.handle.net/1822/22006
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1420-3049
10.3390/molecules17043834
22456543
www.mdpi.com/journal/molecules
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799132976215228416