Alvarez Natalia, Rocha Analu, Collazo Victoria, Ellena Javier, Costa-Filho Antonio J, Batista Alzir A, Facchin Gianella
Química Inorgánica, Departamento Estrella Campos, Facultad de Química, Universidad de la República, Montevideo 11800, Uruguay.
Departamento de Química, Federal University of São Carlos, CP 676, São Carlos 13565-905, SP, Brazil.
Pharmaceutics. 2023 Apr 27;15(5):1345. doi: 10.3390/pharmaceutics15051345.
Coordination complexes may act as anticancer agents. Among others, the formation of the complex may facilitate the ligand uptake by the cell. Searching for new copper compounds with cytotoxic activity, the complex Cu-dipicolinate was studied as a neutral scaffold to form ternary complexes with diimines. A series of [Cu(dipicolinate)(diimine)] complexes (where diimine: Phenanthroline, phen, 5-NO-phenanthroline, 4-methyl-phenanthroline, neocuproine, 3,4,7,8-tetramethyl-phenanthroline, tmp, bathophenanthroline, bipyridine, dimethyl-bipyridine, as well as the ligand 2,2-dipyridil-amine, bam) were synthesized and characterized both in the solid state, including a new crystal structure of [Cu(dipicolinate)(tmp)]·7HO. Their chemistry in aqueous solution was explored by UV/vis spectroscopy, conductivity, cyclic voltammetry, and electron paramagnetic resonance studies. Their DNA binding was analyzed by electronic spectroscopy (determining values), circular dichroism, and viscosity methods. The cytotoxicity of the complexes was assessed on human cancer cell lines MDA-MB-231, MCF-7 (breast, the first triple negative), A549 (lung epithelial) and A2780cis (ovarian, Cisplatin-resistant), and non-tumor cell lines MRC-5 (lung) and MCF-10A (breast). The major species are ternary, in solution and solid state. Complexes are highly cytotoxic as compared to Cisplatin. Complexes containing bam and phen are interesting candidates to study their in vivo activity in triple-negative breast cancer treatment.
配位络合物可作为抗癌剂。其中，络合物的形成可能有助于细胞对配体的摄取。为了寻找具有细胞毒性活性的新型铜化合物，研究了铜-吡啶二甲酸盐络合物作为一种中性支架，用于与二亚胺形成三元络合物。合成了一系列[Cu(吡啶二甲酸盐)(二亚胺)]络合物（其中二亚胺：菲咯啉、phen、5-NO-菲咯啉、4-甲基-菲咯啉、新亚铜试剂、3,4,7,8-四甲基-菲咯啉、tmp、红菲绕啉、联吡啶、二甲基-联吡啶，以及配体2,2-联吡啶胺、bam），并对其进行了固态表征，包括[Cu(吡啶二甲酸盐)(tmp)]·7H₂O的新晶体结构。通过紫外/可见光谱、电导率、循环伏安法和电子顺磁共振研究探索了它们在水溶液中的化学性质。通过电子光谱（测定ε值）、圆二色性和粘度方法分析了它们与DNA的结合情况。评估了这些络合物对人癌细胞系MDA-MB-231、MCF-7（乳腺癌，首个三阴性）、A549（肺上皮细胞）和A2780cis（卵巢癌，顺铂耐药）以及非肿瘤细胞系MRC-5（肺）和MCF-10A（乳腺）的细胞毒性。主要物种在溶液和固态中均为三元。与顺铂相比，这些络合物具有高度细胞毒性。含有bam和phen的络合物是研究其在三阴性乳腺癌治疗中体内活性的有趣候选物。
