Our previously reported copper-based complexes of tropolone show nice antitumor effects, but with high cytotoxicity to normal cells, which is presumably caused by copper ions. Here, we managed to achieve this challenge by using other 3D metals to replace copper ions. We thus prepared four mononuclear 3D metal complexes [M(phen)L2] (M = Mn, Co, Ni, and Zn for 1-4, respectively). Complexes 1 and 4 show selectivity on different cancer cell lines with much lower cytotoxicity to normal cells than cisplatin. The anticancer effects for complexes 2 and 3 on the tested cancer cell lines are very poor. It revealed a tuning effect of different metal ions on the anticancer activities with those for Mn(II) and Zn(II) being much higher than those for Co(II) and Ni(II) in this system. Among them, complex 1 presents a best anticancer effect on HeLa cells comparable to cisplatin. It overcame the afore-mentioned shortage of high cytotoxicity to normal cells for the reported Cu(II) complexes. It revealed from the mechanistic studies that complex 1 mainly induces apoptosis through the mitochondrial pathway by increasing intracellular reactive oxygen species, releasing Ca2+, and activating Caspase 9 and proapoptotic gene Bax.

中文翻译：

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混合配体3d金属配合物的合成和抗癌活性。

我们之前报道的铜基托酚酮配合物显示出良好的抗肿瘤作用，但对正常细胞具有很高的细胞毒性，这大概是由铜离子引起的。在这里，我们设法通过使用其他3D金属来替代铜离子来应对这一挑战。因此，我们制备了四个单核3D金属络合物[M（phen）L2]（M分别为1-4的M = Mn，Co，Ni和Zn）。配合物1和4在不同癌细胞系上显示出选择性，对正常细胞的细胞毒性比顺铂低得多。复合物2和3对测试的癌细胞系的抗癌作用非常差。它揭示了不同金属离子对抗癌活性的调节作用，在该系统中，Mn（II）和Zn（II）的金属离子远高于Co（II）和Ni（II）的金属离子。他们之中，复合物1对HeLa细胞具有最佳的抗癌作用，可与顺铂媲美。对于所报道的Cu（II）配合物，它克服了前述对正常细胞的高细胞毒性的不足。从机理研究中发现，复合物1主要通过增加细胞内活性氧种类，释放Ca2 +并激活Caspase 9和促凋亡基因Bax来通过线粒体途径诱导凋亡。