A novel optically pure dinuclear copper(II) complex of a rosin derivative dehydroabietic acid (DHA, HL) was synthesized and fully characterized. The in vitro antitumor activities of the copper(II) complex Cu2(µ2-O)(L)4(DMF)2 (1) were explored and compared with those of a trinuclear iron(III) complex [Fe3(µ3-O)(L)6(CH3OH)2(CH3O)]·H2O (2). 1 was more cytotoxic than 2, and the in vitro cytotoxicity of 1 was comparable to that of cisplatin and oxaliplatin. The metal coordination improved the cytotoxicity of DHA. 1 could arrest cycle in G1 phase and induce apoptosis in MCF-7 cell. 1 increased reactive oxygen species level, GSSG/GSH ratio, and Ca2+ production, and caused the loss of mitochondrial membrane potential (Δψm) in MCF-7 cells. The up-regulated Bax and down-regulated Bcl-2 expression levels, caspase-9/caspase-3 activation, and the release of Cyt c demonstrate that 1 triggered mitochondria-mediated intrinsic apoptosis in MCF-7 cells. Caspase-8/caspase-4 activation and up-regulated Fas expression indicate that death receptor-mediated extrinsic apoptosis was included. Comet assay and up-regulated γ-H2AX and p53 expressions confirmed that 1 caused DNA damage in MCF-7 cells. Moreover, 1 led to enhancement of the biomarker of lipid peroxidation and the indicator of protein carbonylation in MCF-7 cells. All the results suggest that 1 could kill MCF-7 cells by generating oxidative stress, impairing DNA, promoting lipid peroxidation and protein carbonylation, and inducing apoptosis and autophagy. Furthermore, 1 also displayed antimetastatic activities with inhibition of cell invasion and migration, together with antiangiogenesis properties. On the whole, copper complex based on rosin derivatives is worth developing as metal-based antitumor drugs.

中文翻译：

---

天然松香衍生的手性脱氢松香酸的铜（II）和铁（III）配合物：金属对结构和细胞毒性的影响。

合成并完全表征了新型的松香衍生物脱氢松香酸（DHA，HL）的光学纯双核铜（II）配合物。探索了铜（II）配合物Cu2（µ2-O）（L）4（DMF）2（1）的体外抗肿瘤活性，并将其与三核铁（III）配合物[Fe3（µ3-O） （L）6（CH 3 OH）2（CH 3 O）]·H 2 O（2）。1比2具有更高的细胞毒性，1的体外细胞毒性与顺铂和奥沙利铂相当。金属配位改善了DHA的细胞毒性。1可以阻止G1期的周期并诱导MCF-7细胞凋亡。1增加了活性氧水平，GSSG / GSH比和Ca2 +的产生，并导致MCF-7细胞线粒体膜电位（Δψm）的损失。上调Bax和下调Bcl-2表达水平，caspase-9 / caspase-3激活，Cyt c的释放证明1触发了MCF-7细胞中的线粒体介导的内在凋亡。Caspase-8 / caspase-4激活和Fas表达上调表明，包括死亡受体介导的外源性细胞凋亡。彗星试验以及γ-H2AX和p53表达的上调证实1引起MCF-7细胞DNA损伤。此外，1导致脂质过氧化的生物标志物的增强和MCF-7细胞中蛋白质羰基化的指示剂。所有结果表明1可以通过产生氧化应激，破坏DNA，促进脂质过氧化和蛋白质羰基化以及诱导细胞凋亡和自噬来杀死MCF-7细胞。此外，1还显示出具有抑制细胞侵袭和迁移的抗转移活性，以及​​抗血管生成特性。总体上，