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New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death
| Resumo: | New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-b]pyridine, using copper (C–O) or palladium (C–N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-b]pyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCT15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI50 concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI50 values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI50 concentrations showing to be the most promising as antitumoral. |
|---|---|
| Autores principais: | Queiroz, Maria João R.P. |
| Outros Autores: | Peixoto, Daniela; Calhelha, Ricardo C.; Soares, Pedro; Santos, Tiago; Lima, Raquel T.; Campos, Joana F.; Abreu, Rui M.V.; Ferreira, Isabel C.F.R.; Vasconcelos, M. Helena |
| Assunto: | Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| Ano: | 2013 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Instituto Politécnico de Bragança |
| Idioma: | inglês |
| Origem: | Biblioteca Digital do IPB |
| _version_ | 1863850748393029632 |
|---|---|
| author | Queiroz, Maria João R.P. |
| author2 | Peixoto, Daniela Calhelha, Ricardo C. Soares, Pedro Santos, Tiago Lima, Raquel T. Campos, Joana F. Abreu, Rui M.V. Ferreira, Isabel C.F.R. Vasconcelos, M. Helena |
| author2_role | author author author author author author author author author |
| author_facet | Queiroz, Maria João R.P. Peixoto, Daniela Calhelha, Ricardo C. Soares, Pedro Santos, Tiago Lima, Raquel T. Campos, Joana F. Abreu, Rui M.V. Ferreira, Isabel C.F.R. Vasconcelos, M. Helena |
| author_role | author |
| contributor_name_str_mv | Biblioteca Digital do IPB |
| country_str | PT |
| creators_json_str | [{\"Person.name\":\"Queiroz, Maria João R.P.\"},{\"Person.name\":\"Peixoto, Daniela\"},{\"Person.name\":\"Calhelha, Ricardo C.\",\"Person.identifier.orcid\":\"0000-0002-6801-4578\"},{\"Person.name\":\"Soares, Pedro\"},{\"Person.name\":\"Santos, Tiago\"},{\"Person.name\":\"Lima, Raquel T.\"},{\"Person.name\":\"Campos, Joana F.\"},{\"Person.name\":\"Abreu, Rui M.V.\",\"Person.identifier.orcid\":\"0000-0002-7745-8015\"},{\"Person.name\":\"Ferreira, Isabel C.F.R.\",\"Person.identifier.orcid\":\"0000-0003-4910-4882\"},{\"Person.name\":\"Vasconcelos, M. Helena\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Biblioteca Digital do IPB |
| datacite.creators.creator.creatorName.fl_str_mv | Queiroz, Maria João R.P. Peixoto, Daniela Calhelha, Ricardo C. Soares, Pedro Santos, Tiago Lima, Raquel T. Campos, Joana F. Abreu, Rui M.V. Ferreira, Isabel C.F.R. Vasconcelos, M. Helena |
| datacite.date.Accepted.fl_str_mv | 2013-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2014-01-27T14:53:56Z |
| datacite.date.embargoed.fl_str_mv | 2014-01-27T14:53:56Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| datacite.titles.title.fl_str_mv | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| dc.contributor.none.fl_str_mv | Biblioteca Digital do IPB |
| dc.creator.none.fl_str_mv | Queiroz, Maria João R.P. Peixoto, Daniela Calhelha, Ricardo C. Soares, Pedro Santos, Tiago Lima, Raquel T. Campos, Joana F. Abreu, Rui M.V. Ferreira, Isabel C.F.R. Vasconcelos, M. Helena |
| dc.date.Accepted.fl_str_mv | 2013-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2014-01-27T14:53:56Z |
| dc.date.embargoed.fl_str_mv | 2014-01-27T14:53:56Z |
| dc.format.none.fl_str_mv | application/pdf application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10198/9177 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| dc.title.fl_str_mv | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | New fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-b]pyridine, using copper (C–O) or palladium (C–N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-b]pyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCT15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI50 concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI50 values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI50 concentrations showing to be the most promising as antitumoral. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://bibliotecadigital.ipb.pt/bitstreams/219866d2-5652-44a0-9684-91f7c2438a78/download |
| funding.funder.alternateName_str_mv | FCT FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.identifier_str_mv | PTDC/QUI-QUI/111060/2009 PEst-OE/AGR/UI0690/2011 SFRH/BPD/68344/2010 |
| funding.name_str_mv | 5876-PPCDTI 6817 - DCRRNI ID SFRH |
| funding_str_mv | PTDC/QUI-QUI/111060/2009 info:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FQUI-QUI%2F111060%2F2009/PT PEst-OE/AGR/UI0690/2011 info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FAGR%2FUI0690%2F2011/PT SFRH/BPD/68344/2010 info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F68344%2F2010/PT |
| id | ipb_ce4c46a02bc6ec2fc09dadadc2c2bb95 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10198/9177 |
| instacron_str | ipb |
| institution | Instituto Politécnico de Bragança |
| instname_str | Instituto Politécnico de Bragança |
| language | eng |
| network_acronym_str | ipb |
| network_name_str | Biblioteca Digital do IPB |
| oai_identifier_str | oai:bibliotecadigital.ipb.pt:10198/9177 |
| organization_str_mv | urn:organizationAcronym:ipb |
| person_str_mv | Queiroz, Maria João R.P. Peixoto, Daniela Calhelha, Ricardo C. Calhelha, Ricardo C. https://www.ciencia-id.pt/F313-E3CE-554E F313-E3CE-554E http://orcid.org/0000-0002-6801-4578 0000-0002-6801-4578 Soares, Pedro Santos, Tiago Lima, Raquel T. Campos, Joana F. Abreu, Rui M.V. Abreu, Rui M.V. https://www.ciencia-id.pt/0F19-0DE2-12A2 0F19-0DE2-12A2 http://orcid.org/0000-0002-7745-8015 0000-0002-7745-8015 Ferreira, Isabel C.F.R. Ferreira, Isabel C.F.R. https://www.ciencia-id.pt/9418-CF95-9919 9418-CF95-9919 http://orcid.org/0000-0003-4910-4882 0000-0003-4910-4882 Vasconcelos, M. Helena |
| publishDate | 2013 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | Biblioteca Digital do IPB |
| repository_id_str | urn:repositoryAcronym:ipb |
| service_str_mv | urn:repositoryAcronym:ipb |
| spelling | engElsevierporNew fluorinated and methoxylated di(hetero)arylethers and di(hetero)arylamines were prepared functionalizing the 7-position of the thieno[3,2-b]pyridine, using copper (C–O) or palladium (C–N) catalyzed couplings, respectively, of the 7-bromothieno[3,2-b]pyridine, also prepared, with ortho, meta and para fluoro or methoxy phenols and anilines. The compounds obtained were evaluated for their growth inhibitory activity on the human tumor cell lines MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), HCT15 (colon carcinoma), HepG2 (hepatocellular carcinoma) and HeLa (cervical carcinoma). The most active compounds, a di(hetero)arylether with a methoxy group in the meta position relative to the ether function and two di(hetero)arylamines with a methoxy group either in the ortho or in the meta position relative to the NH, were further tested at their GI50 concentrations on NCI-H460 cells causing pronounced alterations in the cell cycle profile and a strong and significant increase in the programmed death of these cells. The fluorinated and the other methoxylated compounds did not show important activity, presenting high GI50 values in all the cell lines tested. Furthermore, the hepatotoxicity of the compounds was assessed using porcine liver primary cells (PLP2), established by some of us. Results showed that one of the most active compounds was not toxic to the non-tumor cells at their GI50 concentrations showing to be the most promising as antitumoral.application/pdfapplication/pdfporNew di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell deathQueiroz, Maria João R.P.Peixoto, DanielaPersonalCalhelha, Ricardo C.DSpacehttp://dspace.org/items/2d5d1a41-7561-4a01-871c-b4c97da35053DSpacehttp://dspace.org/items/2d5d1a41-7561-4a01-871c-b4c97da35053CalhelhaRicardo C.Ciência IDhttps://www.ciencia-id.ptF313-E3CE-554EORCIDhttp://orcid.org0000-0002-6801-4578Researcher IDhttps://www.researcherid.comJ-2172-2014Scopus Author IDhttps://www.scopus.com6507978333Soares, PedroSantos, TiagoLima, Raquel T.Campos, Joana F.PersonalAbreu, Rui M.V.DSpacehttp://dspace.org/items/cadb03a4-5e60-4745-b35f-fc3a97c071bcDSpacehttp://dspace.org/items/cadb03a4-5e60-4745-b35f-fc3a97c071bcAbreuRui M.V.Ciência IDhttps://www.ciencia-id.pt0F19-0DE2-12A2ORCIDhttp://orcid.org0000-0002-7745-8015Scopus Author IDhttps://www.scopus.com7003290613PersonalFerreira, Isabel C.F.R.DSpacehttp://dspace.org/items/bd0d1537-2e03-41fb-b27a-140af9c35db8DSpacehttp://dspace.org/items/bd0d1537-2e03-41fb-b27a-140af9c35db8FerreiraIsabel C.F.R.Ciência IDhttps://www.ciencia-id.pt9418-CF95-9919ORCIDhttp://orcid.org0000-0003-4910-4882Researcher IDhttps://www.researcherid.comE-8500-2013Scopus Author IDhttps://www.scopus.com36868826600Vasconcelos, M. HelenaHostingInstitutionOrganizationalBiblioteca Digital do IPBe-mailmailto:dspace@ipb.ptdspace@ipb.ptISSNIsPartOf0223-52342014-01-27T14:53:56Z20132013-01-01T00:00:00ZHandlehttp://hdl.handle.net/10198/9177http://purl.org/coar/access_right/c_abf2open accessDi(hetero)arylethersDi(hetero)arylaminesThieno[3,2-b]pyridinesMetal-catalyzed couplingsTumor and nontumor cells growth inhibitionCell cycle analysis and cell death728972 bytes1087663 bytesFundação para a Ciência e a TecnologiaNew antitumor and antiangiogenic heterocyclic compounds: synthesis, molecular modeling, screening of enzymatic inhibition and studies in tumor and endothelial cell lines with tyrosine kinase membrane receptors as targetsinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FQUI-QUI%2F111060%2F2009/PTPTDC/QUI-QUI/111060/20095876-PPCDTICrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaStrategic Project - UI 690 - 2011-2012info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/PEst-OE%2FAGR%2FUI0690%2F2011/PTPEst-OE/AGR/UI0690/20116817 - DCRRNI IDCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaNew antitumor and/or anti-angiogenic heterocyclic compounds: Synthesis, molecular modelling and inhibition enzymatic assays using tyrosine kinase membrane growth factor receptorsinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F68344%2F2010/PTSFRH/BPD/68344/2010SFRHCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://bibliotecadigital.ipb.pt/bitstreams/219866d2-5652-44a0-9684-91f7c2438a78/downloadhttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://bibliotecadigital.ipb.pt/bitstreams/870ab451-0782-46fe-b402-bbc99f005aa5/downloadEuropean Journal of Medicinal Chemistry69855862 |
| spellingShingle | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death Queiroz, Maria João R.P. Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| subject.fl_str_mv | Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| title | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| title_full | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| title_fullStr | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| title_full_unstemmed | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| title_short | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| title_sort | New di(hetero)arylethers and di(hetero)arylamines in the thieno[3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death |
| topic | Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| topic_facet | Di(hetero)arylethers Di(hetero)arylamines Thieno[3,2-b]pyridines Metal-catalyzed couplings Tumor and nontumor cells growth inhibition Cell cycle analysis and cell death |
| url | http://hdl.handle.net/10198/9177 |
| visible | 1 |
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