Aim: To develop novel anti-breast cancer agents and discuss the structure-activity relationship of bis-isatin scaffolds.

Background: Breast cancer is the most common invasive cancer and the second leading cause of cancer death in women after lung cancer. Bis-isatin scaffolds possess potential anti-breast cancer activity, and some of them such as Indirubin could induce cancer cells apoptosis via multiply mechanisms.

Objective: The primary objective of this study was to evaluate the potential of bis-isatin scaffolds with alkyl/ether linkers between the two isatin moieties against different human breast cancer cell lines including MCF-7, AU565, MDA-MB-231, MDA-MB-435 and MDA-MB-468 cells.

Methods: The synthesized bis-isatin scaffolds with alkyl/ether linker between the two isatin moieties were evaluated for their in vitro activity against MCF-7, AU565, MDA-MB-231, MDA-MB-435, and MDA-MB-468 human breast cancer cell lines by MTT assay.

Results: All the synthesized compounds (IC50: 38.3-197.6 µM) possess considerable activity against MCF-7, AU565, MDA-MB-231, MDA-MB-435, and MDA-MB-468 human breast cancer cell lines, and the most potent compound 4e (IC50: 38.3-63.5 µM) was no inferior to Cisplatin (IC50: 20.1-38.6 μM) against the five tested human breast cancer cell lines.

Conclusion: All the synthesized bis-isatin scaffolds were active against a panel of breast cancer cell lines, highlighting the significance of exploring the bis-isatin scaffolds to fight against breast cancers. The enriched structure-activity relationship may set up the direction for the rational design and development of novel bis-isatin scaffolds with higher efficiency.

目的：开发新型抗乳腺癌药物，探讨双-isatin支架的构效关系。

背景：乳腺癌是女性中最常见的浸润性癌症，是仅次于肺癌的第二大癌症死亡原因。Bis-isatin支架具有潜在的抗乳腺癌活性，其中一些（如靛玉红）可以通过多种机制诱导癌细胞凋亡。

目的：这项研究的主要目的是评估在两个isatin部分之间具有烷基/醚连接基的双isatin支架对不同的人乳腺癌细胞系MCF-7，AU565，MDA-MB-231，MDA- MB-435和MDA-MB-468细胞。

方法：评估两个isatin部分之间具有烷基/醚连接基的双isatin支架对MCF-7，AU565，MDA-MB-231，MDA-MB-435和MDA-MB-468的体外活性。 MTT法检测人乳腺癌细胞系。

结果：所有合成的化合物（IC50：38.3-197.6 µM）对MCF-7，AU565，MDA-MB-231，MDA-MB-435和MDA-MB-468人乳腺癌细胞系均具有相当大的活​​性，并且对于五种测试的人乳腺癌细胞系，最有效的化合物4e（IC50：38.3-63.5 µM）不逊于顺铂（IC50：20.1-38.6 µM）。

结论：所有合成的双-isatin支架均对一组乳腺癌细胞系具有活性，突出了探索双-isatin支架对抗乳腺癌的意义。丰富的构效关系可以为新型双-isatin支架的合理设计和开发提供方向。