Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran; Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran.
Bioorg Med Chem Lett. 2021 Jul 1;43:128107. doi: 10.1016/j.bmcl.2021.128107. Epub 2021 May 13.
Triple-Negative Breast Cancer (TNBC) is a highly aggressive form of breast cancer. The high rate of metastasis associated with TNBC is attributed to its multidrug resistance, making the treatment of this metastatic condition difficult. The development of metal-based antitumor agents was launched with the discovery of cisplatin, followed by the development of related antitumor drugs such as carboplatin and oxaliplatin. Yet, the severe side effects of this approach represent a limitation for its clinical use. The current search for new metal-based antitumor agents possessing less severe side effects than these platinum-based complexes has focused on various complexes of nickel and palladium, the group 10 congeners of platinum. In this work, we have prepared a series of SCS-type pincer complexes of nickel and palladium featuring a stable meta-phenylene central moiety and two chelating but labile thioamide donor moieties at the peripheries of the ligand. We have demonstrated that the complexes in question, namely LNiCl, LNiBr, LPdCl, LPdCl, and LPdCl, are active on the proliferation of estrogen-dependent breast tumor cells (MCF-7 and MC4L2) and triple-negative breast cancer (4 T1). Among the complexes studied, the palladium derivatives were found to be much safer anticancer agents than nickel counterparts; these were thus selected for further investigations for their effects on tumor cell adhesion and migration as well. The results of our studies show that palladium complexes are effective for inhibiting TNBC 4 T1 cells adhesion and migration. Finally, the HOMO and LUMO analysis was used to determine the reactivity and charge transfer within the compounds.
三阴性乳腺癌（TNBC）是一种侵袭性很强的乳腺癌。TNBC 转移率高与其多药耐药性有关，这使得转移性疾病的治疗变得困难。顺铂的发现推动了金属抗肿瘤药物的发展，随后开发了相关的抗肿瘤药物，如卡铂和奥沙利铂。然而，这种方法的严重副作用限制了其临床应用。目前，人们正在寻找新的金属抗肿瘤药物，这些药物的副作用比铂类复合物的副作用要小，研究重点是铂的同族元素镍和钯的各种复合物。在这项工作中，我们制备了一系列具有稳定间苯撑中心部分和配位但不稳定硫代酰胺供体部分的镍和钯 SCS 型夹钳配合物。我们已经证明，所研究的配合物，即 LNiCl、LNiBr、LPdCl、LPdCl 和 LPdCl，对依赖雌激素的乳腺癌肿瘤细胞（MCF-7 和 MC4L2）和三阴性乳腺癌（4 T1）的增殖具有活性。在所研究的配合物中，钯衍生物被发现是比镍类似物更安全的抗癌剂；因此，选择这些钯衍生物进一步研究其对肿瘤细胞黏附和迁移的影响。我们的研究结果表明，钯配合物能有效抑制三阴性乳腺癌 4 T1 细胞的黏附和迁移。最后，利用 HOMO 和 LUMO 分析来确定化合物内的反应性和电荷转移。
