Cisplatin and other platinum‐based drugs are well‐known valid anticancer drugs. However, during chemotherapy, the presence of numerous side effects and the onset of frequent phenomena of resistance has pushed many research groups to devise new metal‐based compounds holding improved anticancer properties and fewer undesired effects. Amongst the variety of synthesized compounds, significant antiproliferative effects have been obtained by employing organometallic compounds, particularly those based on silver and gold. With this in mind, we synthesized four compounds, two silver complexes and two gold complexes, with good inhibitory effects on the in vitro proliferation of breast and ovarian cancer‐cell models. The antitumor activity of the most active compound, that is, AuL4, was found to be ninefold higher than that of cisplatin, and this compound induced dramatic morphological changes in HeLa cells. AuL4 induced PARP‐1 cleavage, caspases 3/7 and 9 activation, mitochondria disruption, cytochrome c release in cancer‐cell cytoplasm, and the intracellular production of reactive oxygen species. Thus, AuL4 treatment caused cancer‐cell death by the intrinsic apoptotic pathway, whereas no cytotoxic effects were recorded upon treating non‐tumor cell lines. The reported outcomes may be an important contribution to the expanding knowledge of medicinal bio‐organometallic chemistry and enlarge the available anticancer toolbox, offering improved features, such as higher activity and/or selectivity, and opening the way to new discoveries and applications.

中文翻译：

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新型金银银复合物具有抗肿瘤作用，可触发依赖于活性氧物种的内在凋亡途径

顺铂和其他铂类药物是众所周知的有效抗癌药物。但是，在化学疗法中，许多副作用的出现和频繁出现的耐药现象促使许多研究小组设计出新的金属基化合物，这些化合物具有改进的抗癌特性，并减少了不良作用。在各种合成的化合物中，通过使用有机金属化合物，特别是基于银和金的有机金属化合物，已经获得了显着的抗增殖作用。考虑到这一点，我们合成了四种化合物，两种银配合物和两种金配合物，对乳腺癌和卵巢癌细胞模型的体外增殖具有良好的抑制作用。活性最高的化合物Au L4的抗肿瘤活性被发现比顺铂高9倍，并且该化合物在HeLa细胞中引起了明显的形态变化。Au L4诱导PARP-1裂解，胱天蛋白酶3/7和9激活，线粒体破坏，癌细胞细胞质中的细胞色素c释放以及细胞内活性氧的产生。因此，Au L4处理通过内在的凋亡途径导致癌细胞死亡，而在治疗非肿瘤细胞系时未见细胞毒性作用。报告的结果可能是对药物生物金属有机化学知识的不断拓展的重要贡献，并扩大了可用的抗癌工具箱，提供了改进的功能，例如更高的活性和/或选择性，并为新的发现和应用开辟了道路。