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its insensitivity to conventional drugs. Zinc is an important trace element for homeostasis, and its Schiff base metal complexes have shown promise in treating advanced tumors. In this study, four new heteroleptic Zn(II) complexes (1\u20134) with Schiff bases were synthesized, characterized, and evaluated for their activity in BC cells. Methods: Compounds were synthesized, characterized, and their crystal structures were determined. Biological activity was assessed using MTT, clonogenic, scratch wound healing, caspase 3 and 8 activity, qPCR, and chemosensitization assays. Results: The complexes exhibited cytotoxicity against MCF-7 (luminal BC), MDA-MB-453 (HER2-positive BC), and MDA-MB-231 (TNBC) cell lines, with IC50 values ranging from 0.01 to 20 \u00b5M. Complex 4 showed reduced cytotoxicity toward non-tumor cell lines. This, complexation with Zn(II) increased the cytotoxicity of the ligands, a trend not observed for complexes 1\u20133. Due to its favorable profile, complex 4 was selected for further assays, in which it inhibited colony formation and the cell migration of TNBC cells in a dose-dependent manner. Furthermore, this compound induced cell death independently of caspases, decreasing the activity of caspase 8. Interestingly, complex 4 sensitized TBNC cells to doxorubicin and paclitaxel, possibly modulating the epithelial\u2013mesenchymal transition mechanism, as evidenced by increased CDH1 expression. Conclusions: Results suggest the potential of complex 4 in sensitizing aggressive BC cells to chemotherapy, proving to be a promising alternative in cases of therapeutic failure.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121610","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T11:17:22Z","timestamp":1734520642000},"page":"1610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6665-1228","authenticated-orcid":false,"given":"Raiane Aparecida dos Santos","family":"Machado","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Patos de Minas 38700-002, MG, Brazil"}]},{"given":"Raoni Pais","family":"Siqueira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Patos de Minas 38700-002, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8078-6282","authenticated-orcid":false,"given":"Fernanda Cardoso","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Patos de Minas 38700-002, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-5889","authenticated-orcid":false,"given":"Andr\u00e9 Carlos Pereira de","family":"Matos","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Patos de Minas 38700-002, MG, Brazil"}]},{"given":"Dayanne Silva","family":"Borges","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Patos de Minas 38700-002, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-3986","authenticated-orcid":false,"given":"Gislaine Gon\u00e7alves","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberl\u00e2ndia, Patos de Minas 38700-002, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0817-2141","authenticated-orcid":false,"given":"Thais Cristina Prado de","family":"Souza","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3472-4026","authenticated-orcid":false,"given":"Rafael Aparecido Carvalho","family":"Souza","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Federal University of Uberl\u00e2ndia, Uberl\u00e2ndia 38400-902, MG, Brazil"}]},{"given":"Clayton Rodrigues de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of S\u00e3o Carlos, Rodovia Washington Lu\u00eds, km 235, S\u00e3o Carlos 13565-905, SP, Brazil"}]},{"given":"Ant\u00f4nio G.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of S\u00e3o Carlos, Rodovia Washington Lu\u00eds, km 235, S\u00e3o Carlos 13565-905, SP, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-9481","authenticated-orcid":false,"given":"Pedro Ivo da Silva","family":"Maia","sequence":"additional","affiliation":[{"name":"Bioactive Compounds Development Research Group, Federal University of Triangulo Mineiro, Av. 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