Novel antitumor copper(ii) complexes designed to act through synergistic mechanisms of action, due to the presence of an NMDA receptor ligand and copper in the same chemical entity,New Journal of Chemistry

当前位置： X-MOL 学术 › New J. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Novel antitumor copper(ii) complexes designed to act through synergistic mechanisms of action, due to the presence of an NMDA receptor ligand and copper in the same chemical entity
New Journal of Chemistry ( IF 2.7 ) Pub Date : 2018-06-12 00:00:00 , DOI: 10.1039/c8nj01763h
Maria Beatrice Morelli _{1,

2,

3,

4,

5} , Consuelo Amantini _{3,

4,

5,

6} , Giorgio Santoni _{1,

2,

3,

4,

5} , Maura Pellei _{3,

4,

5,

7,

8} , Carlo Santini _{3,

4,

5,

7,

8} , Cristina Cimarelli _{3,

4,

5,

7,

8} , Enrico Marcantoni _{3,

4,

5,

7,

8} , Marino Petrini _{3,

4,

5,

7,

8} , Fabio Del Bello _{1,

3,

4,

5,

9} , Gianfabio Giorgioni _{1,

3,

4,

5,

9} , Alessandro Piergentili _{1,

3,

4,

5,

9} , Wilma Quaglia _{1,

3,

4,

5,

9}

Affiliation

In the present article the 1,4-dioxane derivative 1, a potent noncompetitive NMDA receptor antagonist, showed cytotoxic activity in the MCF7 breast cancer cell line significantly higher than those of the functionally related compounds (S)-(+)-ketamine and MK-801. Encouraged by this result and considering that copper complexes have been highlighted to be promising anticancer agents, the NMDA receptor ligand 1 was linked to the bifunctionalizable species 2 and 3, affording the conjugated derivatives 4 and 5 that were used for the preparation of the stable Cu(II) complexes 6 and 7. All the compounds were evaluated against a panel of human cancer cell lines derived from solid tumors. Complex 7 showed the best antitumor activity in all the studied cell lines. This result suggests that 7 might act through synergistic mechanisms of action due to the presence of the NMDA ligand 1 and copper(II) in the same chemical entity. Furthermore, the cellular mechanisms affected by complex 7 were assessed through cytofluorimetric and western blot analyses. Data suggested the induction of cell death through paraptosis mediated by endoplasmic reticulum (ER) stress.

中文翻译：

由于在同一化学实体中存在NMDA受体配体和铜，新型的抗肿瘤铜（ii）配合物旨在通过协同作用机制发挥作用

在本文中，有效的非竞争性NMDA受体拮抗剂1,4-二恶烷衍生物1在MCF7乳腺癌细胞系中显示出明显高于功能相关化合物（S）-（+）-氯胺酮和MK的细胞毒活性。-801。受此结果的鼓舞，并考虑到铜络合物已被强调是有前途的抗癌药物，NMDA受体配体1与双功能性物质2和3连接，提供了用于制备稳定Cu的共轭衍生物4和5。（II）配合物6和7。针对源自实体瘤的一组人类癌细胞系评估了所有化合物。复合物7在所有研究的细胞系中均显示出最佳的抗肿瘤活性。该结果表明，由于NMDA配体1和铜（II）在同一化学实体中的存在，因此7可能通过协同作用机制起作用。此外，通过细胞荧光分析和蛋白质印迹分析评估了受复合物7影响的细胞机制。数据表明通过内质网（ER）应激介导的截瘫诱导细胞死亡。

更新日期：2018-06-12

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11