{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T19:00:30Z","timestamp":1771268430406,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:00:00Z","timestamp":1670025600000},"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 Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/00313\/2020"],"award-info":[{"award-number":["UIDP\/00313\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UID\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/QUI-QOR\/0103\/2021"],"award-info":[{"award-number":["PTDC\/QUI-QOR\/0103\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FCT, I.P.\/MCTES","award":["UIDB\/00313\/2020"],"award-info":[{"award-number":["UIDB\/00313\/2020"]}]},{"name":"FCT, I.P.\/MCTES","award":["UIDP\/00313\/2020"],"award-info":[{"award-number":["UIDP\/00313\/2020"]}]},{"name":"FCT, I.P.\/MCTES","award":["UID\/QUI\/50006\/2020"],"award-info":[{"award-number":["UID\/QUI\/50006\/2020"]}]},{"name":"FCT, I.P.\/MCTES","award":["PTDC\/QUI-QOR\/0103\/2021"],"award-info":[{"award-number":["PTDC\/QUI-QOR\/0103\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Herein, the synthesis and anticancer activity evaluation of a series of novel \u03b2-carbolines is reported. The reactivity of nitrosoalkenes towards indole was explored for the synthesis of novel tryptophan analogs where the carboxylic acid was replaced by a triazole moiety. This tryptamine was used in the synthesis of 3-(1,2,3-triazol-4-yl)-\u03b2-carbolines via Pictet\u2013Spengler condensation followed by an oxidative step. A library of compounds, including the novel 3-(1,2,3-triazol-4-yl)-\u03b2-carbolines as well as methyl \u03b2-carboline-3-carboxylate and 3-tetrazolyl-\u03b2-carboline derivatives, was evaluated for their antiproliferative activity against colorectal cancer cell lines. The 3-(1H-tetrazol-5-yl)-\u03b2-carbolines stood out as the most active compounds, with values of half-maximal inhibitory concentration (IC50) ranging from 3.3 \u00b5M to 9.6 \u00b5M against colorectal adenocarcinoma HCT116 and HT29 cell lines. The results also revealed a mechanism of action independent of the p53 pathway. Further studies with the 3-tetrazolyl-\u03b2-carboline derivative, which showed high selectivity for cancer cells, revealed IC50 values below 8 \u03bcM against pancreatic adenocarcinoma PANC-1, melanoma A375, hepatocarcinoma HEPG2, and breast adenocarcinoma MCF-7 cell lines. Collectively, this work discloses the 3-tetrazolyl-\u03b2-carboline derivative as a promising anticancer agent worthy of being further explored in future works.<\/jats:p>","DOI":"10.3390\/ph15121510","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T01:42:21Z","timestamp":1670204541000},"page":"1510","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["3-(1,2,3-Triazol-4-yl)-\u03b2-Carbolines and 3-(1H-Tetrazol-5-yl)-\u03b2-Carbolines: Synthesis and Evaluation as Anticancer Agents"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-3930","authenticated-orcid":false,"given":"Jo\u00e3o L. P.","family":"Ribeiro","sequence":"first","affiliation":[{"name":"University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences, Department of Chemistry, 3004-535 Coimbra, Portugal"}]},{"given":"Joana B.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-5667","authenticated-orcid":false,"given":"Susana M. M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences, Department of Chemistry, 3004-535 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9531-4939","authenticated-orcid":false,"given":"Luc\u00edlia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3256-4954","authenticated-orcid":false,"given":"Teresa M. V. D.","family":"Pinho e Melo","sequence":"additional","affiliation":[{"name":"University of Coimbra, Coimbra Chemistry Centre-Institute of Molecular Sciences, Department of Chemistry, 3004-535 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.bmcl.2015.01.058","article-title":"Design, synthesis of new \u03b2-carboline derivatives and their selective anti-HIV-2 activity","volume":"25","author":"Ashok","year":"2015","journal-title":"Bioorg. Med. Chem. 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