Department of Inorganic Chemistry, Faculty of Chemistry, Jagiellonian University in Kraków, Gronostajowa 2, 30-387 Krakow, Poland.
Metallomics. 2020 May 27;12(5):784-793. doi: 10.1039/d0mt00019a.
The well-documented cytotoxic activity of coordinatively saturated and substitutionally inert polypyridyl Ru(ii) complexes substantiates their high potency as antiproliferative agents against primary tumors. However, the primary cause of cancer morbidity and mortality responsible for about 90% of cancer deaths is the occurrence of metastasis. Therefore, scientists have to concentrate their efforts on designing compounds affecting not only the primary tumor, but also efficiently inhibiting metastasis. Herein, we report two families of Ru(ii) polypyridyl complexes bearing 2,2'-bipyridine substituted by a semicarbazone 2-formylopyridine moiety as one of the ligands and 4,4'-di-tert-butyl-2,2'-dipyridyl or 4,7-diphenyl-1,10-phenanthroline as auxiliary ligands. These complexes strengthen cells' adherent properties and inhibit the activity of metalloproteinases (MMPs) in vitro, which is relevant in anti-metastatic treatment. The in vitro studies were performed on human lung adenocarcinoma (A549) and human pancreatic cancer (PANC-1) cells, which have a well-documented invasive potential. The induced alteration of the tumor cells' adhesion properties correlated with the high cytotoxic effect exerted by the complexes and their excellent cellular uptake. It was also proved that both complexes directly inhibit M-MP2 and M-MP9 enzyme activities, which are essential for the development of tumor metastasis. The results of this study indicate that the biological properties of polypyridyl Ru(ii) complexes extend beyond the standard cytotoxic activity and represent an important step towards designing new anti-metastatic agents.
配位饱和和取代惰性的多吡啶钌（II）配合物具有明显的细胞毒性活性，这证明了它们作为原发性肿瘤抗增殖剂的高效力。然而，导致 90%癌症死亡的癌症发病率和死亡率的主要原因是转移的发生。因此，科学家们必须集中精力设计不仅能影响原发性肿瘤，而且能有效抑制转移的化合物。在此，我们报告了两类含有 2,2'-联吡啶取代的半缩醛 2-甲酰基吡啶部分的钌（II）多吡啶配合物，作为一个配体和 4,4'-二叔丁基-2,2'-联吡啶或 4,7-二苯基-1,10-菲咯啉作为辅助配体。这些配合物增强了细胞的黏附特性，并在体外抑制了金属蛋白酶（MMPs）的活性，这在抗转移治疗中是相关的。体外研究在具有明确侵袭潜力的人肺腺癌细胞（A549）和人胰腺癌细胞（PANC-1）上进行。肿瘤细胞黏附特性的诱导变化与配合物的高细胞毒性作用及其优异的细胞摄取能力相关。还证明了这两种配合物都直接抑制 M-MP2 和 M-MP9 酶的活性，这对肿瘤转移的发展至关重要。这项研究的结果表明，多吡啶钌（II）配合物的生物学性质超出了标准的细胞毒性活性，并代表了设计新的抗转移剂的重要一步。
