Lysosome targeted drugs: rhodamine B modified N^N-chelating ligands for half-sandwich iridium(iii) anticancer complexes†,Inorganic Chemistry Frontiers

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Lysosome targeted drugs: rhodamine B modified N^N-chelating ligands for half-sandwich iridium(iii) anticancer complexes†
Inorganic Chemistry Frontiers ( IF 6.1 ) Pub Date : 2018-08-28 00:00:00 , DOI: 10.1039/c8qi00620b
Wenli Ma _{1,

2,

3,

4,

5} , Zhenzhen Tian _{1,

2,

3,

4,

5} , Shumiao Zhang _{1,

2,

3,

4,

5} , Xiangdong He _{1,

2,

3,

4,

5} , JuanJuan Li _{1,

2,

3,

4,

5} , Xiaorong Xia _{1,

2,

3,

4,

5} , Xiaobing Chen _{1,

2,

3,

4,

5} , Zhe Liu _{1,

2,

3,

4,

5}

Affiliation

We designed and synthesized four rhodamine-modified half-sandwich iridium complexes ([(η⁵-Cp^x)Ir(N^N)Cl]PF₆). The fluorescence properties of the complexes were studied. Excitingly, the cytotoxicity of the complexes was superior to that of cisplatin for both A549 cells and HeLa cells. In particular, for A549 cells, the cytotoxicity of complexes 2 and 3 was 5 or 6-fold higher than that of cisplatin. Interactions with ctDNA and BSA have been investigated. The results show that the interaction with DNA does not seem to be the main anticancer mechanism. A binding experiment between BSA and complexes was carried out using a UV spectrophotometer and a fluorescence spectrophotometer. The catalytic conversion of the coenzyme NADH to NAD⁺ has also been investigated for hydrogen transfer of the complexes. In addition, complex 3 was studied in cell experiments because of its good antiproliferative activity. In addition, the cell distribution and targeting mechanisms of these complexes were studied using confocal microscopy. Complex 3 can induce cell death by blocking the G₀/G₁ phase of the cell cycle, affecting the mitochondrial membrane potential, then entering the cells and specifically targeting lysosomes. These seem to contribute to the anticancer activity of the complexes.

中文翻译：

溶酶体靶向药物：若丹明B修饰的半三明治铱（iii）抗癌复合物的N ^ N螯合配体†

我们设计并合成了4种罗丹明改性半夹心铱络合物（[（η ⁵ -Cp ^X）IR（N ^ N）CL] PF ₆）。研究了配合物的荧光性质。令人兴奋的是，对于A549细胞和HeLa细胞，复合物的细胞毒性均优于顺铂。特别是对于A549细胞，复合物2和3的细胞毒性比顺铂高5到6倍。已经研究了与ctDNA和BSA的相互作用。结果表明，与DNA的相互作用似乎不是主要的抗癌机制。使用紫外分光光度计和荧光分光光度计进行BSA和复合物之间的结合实验。还研究了辅酶NADH向NAD ⁺的催化转化，以实现复合物的氢转移。此外，由于其良好的抗增殖活性，在细胞实验中对复合物3进行了研究。此外，使用共聚焦显微镜研究了这些复合物的细胞分布和靶向机制。配合物3可通过阻断G ₀ / G ₁诱导细胞死亡细胞周期的阶段，影响线粒体膜电位，然后进入细胞并特异性靶向溶酶体。这些似乎有助于复合物的抗癌活性。

更新日期：2018-08-28

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