Design, synthesis and evaluation of 6-aryl-indenoisoquinolone derivatives dual targeting ERα and VEGFR-2 as anti-breast cancer agents.

摘要: The estrogen receptors have played important roles in breast cancer development and progression. Selective receptor modulators, such as Tamoxifen, showed great benefits the treatment prevention of cancer. But disadvantages induction endometrial drug resistance limited their use. Multiple ligand which act at multiple biomolecular targets may exert favorable advantages improved efficacy with lower incidence side effects. In this work, we described synthesis evaluation a series 6-aryl-indenoisoquinolone derivatives dual ERα VEGFR-2 inhibitors. These compounds presented good binding affinity antagonistic activity, well potent inhibitory potency. They also possessed excellent anti-proliferative activities against MCF-7, MDA-MB-231, Ishikawa HUVEC cell lines. Further investigation selective compound 21c that it was able to inhibit activation signaling transduction Raf-1/MAPK/ERK pathway MCF-7 cells.