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金属配合物的合成及抗癌活性。

我们之前报道的托酚酮铜基复合物显示出良好的抗肿瘤作用，但对正常细胞具有高细胞毒性，这可能是由铜离子引起的。在这里，我们通过使用其他 3D 金属替代铜离子来成功应对这一挑战。因此，我们制备了四种单核 3D 金属配合物 [M(phen)L2]（M = Mn、Co、Ni 和 Zn，分别为 1-4）。复合物 1 和 4 显示出对不同癌细胞系的选择性，对正常细胞的细胞毒性比顺铂低得多。复合物 2 和 3 对受试癌细胞系的抗癌作用很差。它揭示了不同金属离子对抗癌活性的调节作用，在该体系中，Mn(II) 和 Zn(II) 的抗癌活性远高于 Co(II) 和 Ni(II)。他们之中，复合物 1 对 HeLa 细胞的抗癌效果与顺铂相当。它克服了上述报道的 Cu(II) 复合物对正常细胞的高细胞毒性的不足。机理研究表明，复合物1主要通过增加细胞内活性氧、释放Ca2+、激活Caspase 9和促凋亡基因Bax，通过线粒体途径诱导细胞凋亡。