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.