In this study, two novel organic ligands, bis(salicylaldehyde)pyrazino-1,10-phenanthroline-7,10-dicarbohydrazide (L) and bis(salicylaldehyde)-1,10-phenanthroline-7,10-dicarbohydrazide (L¹), were synthesized. These ligands were used to react with lanthanide(III) acetate to obtain complexes 1–6, namely, [Dy₅(L)₂(CH₃COO)₅(CH₃OH)(μ₃-OH)(μ₂-OH)(H₂O)]·2CH₃OH (1), [Tb₅(L)₂(CH₃COO)₅(CH₃OH)(μ₃-OH)(μ₂-OH)(H₂O)]·3CH₃OH (2), [Gd₅(L)₂(CH₃COO)₅(CH₃OH)(μ₃-OH)(μ₂-OH)(H₂O)]·3CH₃OH (3), [Dy₅(L¹)₂(μ₂-OH)(μ₃-OH)(CH₃COO)₅(CH₃OH)(H₂O)₂]·2H₂O (4), [Dy₅(L¹)₂(μ₃-OH)(CH₃COO)₆(CH₃OH)₃]·CH₃OH (5), and [Dy₅(L¹)₂(μ₂-OH)₂(μ₃-OH)(CH₃COO)₄(CH₃OH)(H₂O)₂]·CH₃OH (6). Fluorescence studies demonstrated that complexes 1–6 show appreciable fluorescence in the yellow-green region. In vitro antitumor screening revealed that complex 1 exhibits better inhibitory activities than the commercial anticancer drug cisplatin against SK-OV-3 and A549 tumor cell lines, with IC₅₀ values of 8.09 ± 1.25 and 13.26 ± 0.39 μM, respectively. All six complexes showed low cytotoxicity toward normal human liver HL-7702 cells compared with cisplatin. Complexes 1 and 3 induced the highest apoptosis rate of SK-OV-3/DDP cells. They also bind to DNA via an intercalative mode with the binding constant K_q values of 1.6 × 10⁴ and 1.19 × 10⁴ L mol⁻¹, respectively. Confocal fluorescence imaging ascertained that complexes 1 and 3 are primarily localized in the mitochondria. Further studies revealed that these complexes trigger SK-OV-3/DDP cell apoptosis via a mitochondrial dysfunction pathway, which is probably caused by the reduction of the mitochondrial membrane potential and the induction of reactive oxygen species production.

中文翻译：

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线粒体定位的二碳酰肼Ln复合物及其体外抗癌活性的机制

在这项研究中，两个新的有机配体，双（水杨醛）吡嗪并-1,10-菲咯啉-7,10-二邻苯二酰肼（L）和双（水杨醛）-1,10-菲咯啉-7,10-二苯并二酰肼（L ¹） ，被合成。这些配位体被用于与镧系元素发生反应（III）乙酸盐，得到复合物1-6，即，[镝₅（L）₂（CH ₃ COO）₅（CH ₃ OH）（μ ₃ -OH）（μ ₂ -OH ）（H ₂ O）]·2CH ₃ OH（1），[Tb ₅（L）₂（CH ₃ COO）₅（CH ₃OH）（μ ₃ -OH）（μ ₂ -OH）（H ₂ O）]·3CH ₃ OH（2），[钆₅（L）₂（CH ₃ COO）₅（CH ₃ OH）（μ ₃ - OH）（μ ₂ -OH）（H ₂ O）]·3CH ₃ OH（3），[镝₅（L ¹）₂（μ ₂ -OH）（μ ₃ -OH）（CH ₃ COO）₅（CH ₃ OH）（H ₂ O）₂ ]·2H ₂ O（4），[镝₅（L ¹）₂（μ ₃ -OH）（CH ₃ COO）₆（CH ₃ OH）₃ ]·CH ₃ OH（5），和[镝₅（L ¹）₂（μ ₂ - OH）₂（μ ₃ -OH）（CH ₃ COO）₄（CH ₃ OH）（H ₂ O）₂ ]·CH ₃ OH（6）。荧光研究表明，配合物1-6在黄绿色区域显示出可观的荧光。体外抗肿瘤筛选显示，复合物1相对于商业抗癌药顺铂对SK-OV-3和A549肿瘤细胞系表现出更好的抑制活性，IC ₅₀值分别为8.09±1.25和13.26±0.39μM。与顺铂相比，所有六个复合物均对正常人肝HL-7702细胞显示出低细胞毒性。配合物1和3诱导SK-OV-3 / DDP细胞的最高凋亡率。它们还通过嵌入模式与DNA结合，结合常数K _q值为1.6×10 ⁴和1.19×10 ⁴ L mol ^-1， 分别。共聚焦荧光成像确定复合物1和3主要位于线粒体中。进一步的研究表明，这些复合物通过线粒体功能障碍途径触发SK-OV-3 / DDP细胞凋亡，这可能是由于线粒体膜电位降低和活性氧产生的诱导所致。