{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:43Z","timestamp":1760146663587,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"]}]},{"name":"FEDER through COMPETE 2020, POCI and PORL","award":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"]}]},{"name":"PPBI-Portuguese Platform of BioImaging","award":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"]}]},{"name":"FCT","award":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"]}]},{"name":"FCT and UBI","award":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"],"award-info":[{"award-number":["UIDB\/00709\/2020","UIDP\/00709\/2020","022161","POCI-01-0145-FEDER-022122","SFRH\/BD\/148028\/2019","CEEC-INST\/00016\/2021\/CP2828\/CT0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cancer treatment remains a significant challenge, with chemotherapy still being one of the most common therapeutic approaches. Based on our initial studies of symmetric monomethine cyanine dyes, which showed potential against colorectal cancer, this study explored several asymmetric cyanines, aiming to develop more potent and selective antitumor agents, particularly against colorectal cancer. In pursuit of this goal, we have designed, synthesized, and structurally characterized twelve new cyanine dyes. Their antiproliferative effects were then investigated in vitro against both tumor and non-tumor cell lines. Notably, the two most promising dyes in terms of potency and selectivity against Caco-2 colorectal cancer cells were derived from the combination of N-methylbenzoxazole and N-methylquinoline (dye 5), as well as N-ethylbenzothiazole and N-ethyl-6-nitrobenzothiazole (dye 10). The potential mechanisms behind their antiproliferative action were also explored, revealing that both dyes penetrate cells and localize within the cytoplasm and nucleus. Furthermore, dye 5 was found to slightly induce apoptosis without causing significant cell cycle arrest, in contrast to dye 10, which increased the number of cells in the G0\/G1 phase. Interestingly, both dyes exhibited marked topoisomerase II inhibitory effects, particularly cyanine 5, which may further explain their antiproliferative activity. Additionally, drug-likeness properties were predicted for both dyes. Overall, cyanine 5 emerged as the most promising candidate for further investigation as a potential treatment for colorectal cancer.<\/jats:p>","DOI":"10.3390\/molecules29235581","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T07:40:32Z","timestamp":1732606832000},"page":"5581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A New Demand for Improved Selectivity and Potency of Cyanine Dyes as Antiproliferative Agents Against Colorectal Cancer Cells"],"prefix":"10.3390","volume":"29","author":[{"given":"Ana","family":"Maia","sequence":"first","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"},{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"given":"Cathy","family":"Ventura","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-9191","authenticated-orcid":false,"given":"Adriana O.","family":"Santos","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"}]},{"given":"Maria J.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7256-2622","authenticated-orcid":false,"given":"Renato E. F.","family":"Boto","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"},{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-7581","authenticated-orcid":false,"given":"\u00c2ngela","family":"Sousa","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4297-5108","authenticated-orcid":false,"given":"Samuel M.","family":"Silvestre","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"},{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0110-4795","authenticated-orcid":false,"given":"Paulo","family":"Almeida","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"},{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0513-7976","authenticated-orcid":false,"given":"Jo\u00e3o L.","family":"Serrano","sequence":"additional","affiliation":[{"name":"CICS-UBI\u2014Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506 Covilh\u00e3, Portugal"},{"name":"Department of Chemistry, University of Beira Interior, Rua Marqu\u00eas de \u00c1vila e Bolama, 6201-001 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.ejmech.2017.08.070","article-title":"Recent advances in drug discovery of phototherapeutic non-porphyrinic anticancer agents","volume":"142","author":"Dichiara","year":"2017","journal-title":"Eur. J. Med. 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