{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:00:24Z","timestamp":1792033224303,"version":"4.4.0"},"reference-count":0,"publisher":"Bentham Science Publishers Ltd.","issue":"12","funder":[{"DOI":"10.13039\/501100002322","name":"CAPES","doi-asserted-by":"publisher","award":["2014-2018"],"award-info":[{"award-number":["2014-2018"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2016\/08851-0"],"award-info":[{"award-number":["2016\/08851-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"FAPESP","doi-asserted-by":"publisher","award":["2019\/19448-8"],"award-info":[{"award-number":["2019\/19448-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"CNPq","doi-asserted-by":"publisher","award":["2013\/22127-2"],"award-info":[{"award-number":["2013\/22127-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["eurekaselect.com"],"crossmark-restriction":true},"short-container-title":["ACAMC"],"published-print":{"date-parts":[[2021,7,9]]},"abstract":"<jats:sec>\n<jats:title>Background:<\/jats:title>\n<jats:p>Several metal-based molecules that display cytotoxicity against multiple cell lines have\nbeen pursued in an attempt to fight against cancer and to overcome the typical side effects of drugs like cisplatin.\nIn this scenario, ruthenium complexes have been extensively studied due to their activity in both in vitro and in\nvivo biological systems, including various cancer cell strains.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective:<\/jats:title>\n<jats:p>We aimed to develop a method to synthesize novel [Ru(NO)(bpy)<jats:sub>2<\/jats:sub>L<jats:sub>2<\/jats:sub>]<jats:sup>2+<\/jats:sup> complexes containing amino\nacid ligands by using an alternative Click Chemistry approach, namely the copper azide-alkyne cycloaddition\nreaction (CuAAC reaction), to construct nitrosyl\/nitrite complexes bearing a modified lysine residue.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>We synthesized a new ligand by Click Chemistry approach and new compounds bearing the\nunprecedented ligand. Cytotoxicity was assessed by the classical MTT colorimetric assay. MCF-7 and MDAMB-\n231 cells were used as breast cancer cell models. MCF-10 was used as a model of healthy cells.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>Amino acid ligands related to N<jats:sub>3<\/jats:sub>-Lys(Fmoc) and the new pyLys were successfully synthesized by the\ndiazotransfer reaction and the CuAAC reaction, respectively. The latter reaction involves coupling between\nN<jats:sub>3<\/jats:sub>-Lys(Fmoc) and 3ethynylpyridine. Both N<jats:sub>3<\/jats:sub>-Lys(Fmoc) and the new pyLys were introduced into the ruthenium\nbipyridine complex I, or cis-[Ru<jats:sup>II<\/jats:sup>(NO)(NO<jats:sub>2<\/jats:sub>)(bpy)<jats:sub>2<\/jats:sub>]<jats:sup>2+<\/jats:sup>, to generate the common nitro-based complex III, which\nwas further converted to the final complex IV. Results of the MTT assay proved the cytotoxic effect of cis-\n[Ru<jats:sup>II<\/jats:sup>(NO)(pyLysO-)(bpy)<jats:sub>2<\/jats:sub>](PF<jats:sub>6<\/jats:sub>)<jats:sub>2<\/jats:sub> against the mammalian breast cancer cells MCF-7 and MDA-MB231.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>The viability assays revealed that complex IV, bearing a NO group and a modified lysine residue,\nwas able to release NO and cross tumor cell membranes. In this work, Complex IV was observed to be the most\nactive ruthenium bipyridine complex against the mammalian breast cancer cells MCF-7 and MDA-MB231: it\nwas approximately twice as active as cisplatin, whilst complexes I-III proved to be less cytotoxic than complex\nIV. Additional tests using healthy MCF 10A cells showed that complexes II-IV were three- to sixfold less toxic\nthan cisplatin, which suggested that complex IV was selective against cancer cells.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/0929867327666201020155105","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T07:30:41Z","timestamp":1603265441000},"page":"1602-1611","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Improving Cytotoxicity against Breast Cancer Cells by Using Mixed-Ligand Ruthenium(II) Complexes of 2,2'-Bipyridine, Amino Acid, and Nitric Oxide Derivatives as Potential Anticancer Agents"],"prefix":"10.2174","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-2335","authenticated-orcid":true,"given":"Ana P.S.","family":"Gaspari","sequence":"first","affiliation":[{"name":"Instituto Federal do Parana (IFPR), Avenida Jose Felipe Tequinha, 1400, Paranava\u00ed\/PR, 87703-536, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0430-2255","authenticated-orcid":true,"given":"Roberto Santana","family":"da Silva","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, Avenida do Cafe, s\/n, Ribeirao Preto\/SP, 14040- 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2374-8148","authenticated-orcid":true,"given":"Zumira A.","family":"Carneiro","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, Avenida do Cafe, s\/n, Ribeirao Preto\/SP, 14040- 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Rodrigues","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, Avenida do Cafe, s\/n, Ribeirao Preto\/SP, 14040- 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-777X","authenticated-orcid":true,"given":"Ivone","family":"Carvalho","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, Avenida do Cafe, s\/n, Ribeirao Preto\/SP, 14040- 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3930-0919","authenticated-orcid":true,"given":"Laena","family":"Pernomian","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, Avenida do Cafe, s\/n, Ribeirao Preto\/SP, 14040- 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-5558","authenticated-orcid":true,"given":"Lucimara P.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Minas Gerais (UEMG), Avenida Prof. M\u00e1rio Palmerio, 1001, Frutal\/MG, 38200-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7228-0182","authenticated-orcid":true,"given":"Loyanne C.B.","family":"Ramos","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences of Ribeirao Preto, Universidade de Sao Paulo, Avenida do Cafe, s\/n, Ribeirao Preto\/SP, 14040- 903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Aguiar","family":"de Souza","sequence":"additional","affiliation":[{"name":"Instituto de Quimica, Universidade Estadual de Campinas (UNICAMP), Campinas\/SP, 13083-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6773-8083","authenticated-orcid":true,"given":"Andr\u00e9 L.B.","family":"Formiga","sequence":"additional","affiliation":[{"name":"Instituto de Quimica, Universidade Estadual de Campinas (UNICAMP), Campinas\/SP, 13083-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","container-title":["Anti-Cancer Agents in Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/eurekaselect.com\/article\/download\/187040","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.eurekaselect.com\/187040\/article","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eurekaselect.com\/article\/download\/187040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T14:10:48Z","timestamp":1626271848000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.eurekaselect.com\/187040\/article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,9]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,7,9]]}},"alternative-id":["LiveAll1"],"URL":"https:\/\/doi.org\/10.2174\/0929867327666201020155105","relation":{},"ISSN":["1871-5206"],"issn-type":[{"value":"1871-5206","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7,9]]},"assertion":[{"value":"Peer 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History"}},{"value":"2021-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}