{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T11:20:17Z","timestamp":1762341617020,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:00:00Z","timestamp":1615593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/686\/2019-2020","PT\/NMR","SFRH\/BPD\/122871\/2016","SFRH\/BD\/115844\/2016"],"award-info":[{"award-number":["UID\/686\/2019-2020","PT\/NMR","SFRH\/BPD\/122871\/2016","SFRH\/BD\/115844\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["UID\/686\/2019-2020"],"award-info":[{"award-number":["UID\/686\/2019-2020"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Portugal 2020","award":["UID\/686\/2019-2020","PT\/NMR"],"award-info":[{"award-number":["UID\/686\/2019-2020","PT\/NMR"]}]},{"name":"COMPETE 2020","award":["UID\/686\/2019-2020"],"award-info":[{"award-number":["UID\/686\/2019-2020"]}]},{"DOI":"10.13039\/501100004895","name":"European Social Fund","doi-asserted-by":"publisher","award":["SFRH\/BPD\/122871\/2016","SFRH\/BD\/115844\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/122871\/2016","SFRH\/BD\/115844\/2016"]}],"id":[{"id":"10.13039\/501100004895","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Human Capital Operational Programme","award":["SFRH\/BD\/115844\/2016","SFRH\/BPD\/122871\/2016"],"award-info":[{"award-number":["SFRH\/BD\/115844\/2016","SFRH\/BPD\/122871\/2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A series of novel functionalized methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates 2a\u20132h were synthesized by C-C Pd-catalyzed Suzuki-Miyaura cross-coupling of methyl 3-bromothieno[3,2-b]pyridine-2-carboxylate with (hetero)aryl pinacol boranes, trifluoro potassium boronate salts or boronic acids. Their antitumoral potential was evaluated in two triple negative breast cancer (TNBC) cell lines\u2014MDA-MB-231 and MDA-MB-468, by sulforhodamine B assay. Their effects on the non-tumorigenic MCF-12A cells were also evaluated. The results demonstrated that three compounds caused growth inhibition in both TNBC cell lines, with little or no effect against the non-tumorigenic cells. The most promising compound was further studied concerning possible effects on cell viability (by trypan blue exclusion assay), cell proliferation (by bromodeoxyuridine assay) and cell cycle profile (by flow cytometry). The results demonstrated that the GI50 concentration of compound 2e (13 \u03bcM) caused a decreased in MDA-MB-231 cell number, which was correlated with a decreased in the % of proliferating cells. Moreover, this compound increased G0\/G1 phase and decreased S phases, when compared to control cells (although was not statistic significant). Interestingly, compound 2e also reduced tumor size using an in ovo CAM (chick chorioallantoic membrane) model. This work highlights the potential antitumor effect of a novel methyl 3-arylthieno[3,2-b]pyridine-2-carboxylate derivative.<\/jats:p>","DOI":"10.3390\/molecules26061594","type":"journal-article","created":{"date-parts":[[2021,3,14]],"date-time":"2021-03-14T23:52:06Z","timestamp":1615765926000},"page":"1594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis of Novel Methyl 3-(hetero)arylthieno[3,2-b]pyridine-2-carboxylates and Antitumor Activity Evaluation: Studies In Vitro and In Ovo Grafts of Chick Chorioallantoic Membrane (CAM) with a Triple Negative Breast Cancer Cell Line"],"prefix":"10.3390","volume":"26","author":[{"given":"Bruna R.","family":"Silva","sequence":"first","affiliation":[{"name":"Centre of Chemistry, University of Minho, 4710-057 Braga, Portugal"},{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6439-5959","authenticated-orcid":false,"given":"Rita","family":"Rebelo","sequence":"additional","affiliation":[{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4261-1101","authenticated-orcid":false,"given":"Juliana M.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-1917","authenticated-orcid":false,"given":"Cristina P. R.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-4643","authenticated-orcid":false,"given":"M. Helena","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Cancer Drug Resistance Group, IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Biological Sciences, FFUP\u2014Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-8035","authenticated-orcid":false,"given":"Maria-Jo\u00e3o R. P.","family":"Queiroz","sequence":"additional","affiliation":[{"name":"Centre of Chemistry, University of Minho, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s40659-017-0140-9","article-title":"Awareness and current knowledge of breast cancer","volume":"50","author":"Akram","year":"2017","journal-title":"Biol. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R68","DOI":"10.1186\/bcr2635","article-title":"Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer","volume":"12","author":"Prat","year":"2010","journal-title":"Breast Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e841","DOI":"10.1016\/j.clbc.2018.07.023","article-title":"Genetic markers in triple-negative breast cancer","volume":"18","author":"Sporikova","year":"2018","journal-title":"Clin. Breast Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrclinonc.2016.66","article-title":"Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease","volume":"13","author":"Bianchini","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bmcl.2003.10.030","article-title":"Design and SAR of thienopyrimidine and thienopyridine inhibitors of VEGFR-2 kinase activity","volume":"14","author":"Munchhof","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1016\/j.bmcl.2005.07.061","article-title":"Inhibition of Src kinase activity by 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-heteroaryl-thieno[3,2-b]pyridine-6-carbonitriles","volume":"15","author":"Boschelli","year":"2005","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1016\/j.bmcl.2008.04.009","article-title":"A discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases","volume":"18","author":"Claridge","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1016\/j.ejmech.2010.09.014","article-title":"Efficient synthesis of 6-(hetero)arylthieno[3,2-b]pyridines by Suzuki\u2013Miyaura coupling. Evaluation of growth inhibition on human tumor cell lines, SARs and effects on the cell cycle","volume":"45","author":"Queiroz","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.ejmech.2010.11.009","article-title":"Synthesis and evaluation of tumor cell growth inhibition of methyl 3-amino-6-[(hetero)arylethynyl]thieno[3,2-b]pyridine-2-carboxylates. Structure\u2013activity relationships, effects on the cell cycle and apoptosis","volume":"46","author":"Queiroz","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.ejmech.2013.09.023","article-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","volume":"69","author":"Queiroz","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3834","DOI":"10.3390\/molecules17043834","article-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","volume":"17","author":"Calhelha","year":"2012","journal-title":"Molecules"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.tet.2019.01.054","article-title":"Synthesis of novel 8-(het)aryl-6H-pyrano[4\u2032,3\u2032:4,5]thieno[3,2-b] pyridines by 6-endo-dig cyclization of Sonogashira products and halolactonizations with Cu salts\/NXS. Preliminary antitumor evaluation","volume":"75","author":"Rodrigues","year":"2019","journal-title":"Tetrahedron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6497","DOI":"10.1016\/j.bmc.2015.08.010","article-title":"Synthesis, antiangiogenesis evaluation and molecular docking studies of 1-aryl-3-[(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas: Discovery of a new substitution pattern for type II VEGFR-2 Tyr kinase inhibitors","volume":"23","author":"Machado","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","first-page":"1","article-title":"Antiangiogenic 1-aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas inhibit MCF-7 and MDA-MB-231 Human breast cancer cell lines through PI3K\/Akt and MAPK\/Erk pathways","volume":"9999","author":"Machado","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.tetlet.2009.10.138","article-title":"Synthesis of new thieno[3,2-b]pyridine derivatives by palladium-catalyzed couplings and intramolecular cyclizations","volume":"51","author":"Calhelha","year":"2010","journal-title":"Tetrahedron Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1016\/j.tet.2007.01.061","article-title":"Recent advances in organotrifluoroborates chemistry","volume":"63","author":"Stefani","year":"2007","journal-title":"Tetrahedron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1016\/j.tet.2007.12.036","article-title":"Non-conventional methodologies for transition-metal catalysed carbon\u2013carbon coupling: A critical overview. Part 2: The Suzuki reaction","volume":"64","author":"Alonso","year":"2008","journal-title":"Tetrahedron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7528","DOI":"10.3390\/molecules20057528","article-title":"Recent developments in the Suzuki-Miyaura reaction: 2010\u20132014","volume":"20","author":"Maluenda","year":"2015","journal-title":"Molecules."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1039\/C8FO02466A","article-title":"Eucalyptus globulus Labill. decoction extract inhibits the growth of NCI-H460 cells by increasing the p53 levels and altering the cell cycle profile","volume":"10","author":"Teixeira","year":"2019","journal-title":"Food Funct."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Long, S., Resende, D., Kijjoa, A., Silva, A.M.S., Pina, A., Fernandez-Marcelo, T., Vasconcelos, M.H., Sousa, E., and Pinto, M.M.M. (2018). Antitumor activity of quinazolinone alkaloids inspired by marine natural products. Mar. Drugs, 16.","DOI":"10.3390\/md16080261"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0163-7258(98)00044-8","article-title":"Strategies toward the design of novel and selective protein tyrosine kinase inhibitors","volume":"82","author":"Traxler","year":"1999","journal-title":"Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2165\/00003495-200969020-00006","article-title":"Sorafenib: A review of its use in advanced hepatocellular carcinoma","volume":"69","author":"Keating","year":"2009","journal-title":"Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1080\/14656566.2017.1309024","article-title":"Sorafenib for the treatment of breast cancer","volume":"18","author":"Bronte","year":"2017","journal-title":"Expert Opin. on Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.5306\/wjco.v7.i4.331","article-title":"Sorafenib in breast cancer treatment: A systematic review and overview of clinical trials","volume":"7","author":"Zafrakas","year":"2016","journal-title":"World J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.canlet.2010.11.011","article-title":"Thyroid hormone as a regulator of tumor induced angiogenesis","volume":"301","author":"Pinto","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9959","DOI":"10.3390\/ijms13089959","article-title":"Chick chorioallantoic membrane (CAM) assay as an in vivo model to study the effect of newly identified molecules on ovarian cancer invasion and metastasis","volume":"13","author":"Lokman","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1159\/000505521","article-title":"Sorafenib inhibits proliferation, migration and invasion of breast cancer cells","volume":"98","author":"Dattachoudhury","year":"2020","journal-title":"Oncology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10549-013-2668-x","article-title":"Effects of sorafenib on energy metabolism in breast cancer cells: Role of AMPK-mTORC1 signaling","volume":"141","author":"Fumarola","year":"2013","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.nano.2017.12.003","article-title":"PEGylated hyaluronic acid-coated liposome for enhanced in vivo efficacy of sorafenib via active tumor cell targeting and prolonged systemic exposure","volume":"14","author":"Mo","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Long, S., Resende, D., Kijjoa, A., Silva, A.M.S., Fernandes, R., Xavier, C.P.R., Vasconcelos, M.H., Sousa, E., and Pinto, M.M.M. (2019). Synthesis of new proteomimetic quinazolinone alkaloids and evaluation of their neuroprotective and antitumor effects. Molecules, 24.","DOI":"10.3390\/molecules24030534"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat. Protoc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/6\/1594\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:16Z","timestamp":1760160916000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/6\/1594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,13]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["molecules26061594"],"URL":"https:\/\/doi.org\/10.3390\/molecules26061594","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2021,3,13]]}}}