Title:Development of Furo[2,3-b]quinoline Derivatives with Anti-Breast Cancer Property by Targeting Topoisomerase II
Volume: 21
Issue: 12
Author(s): Ying Wang, Na Li, Neng Jiang, Li Chen*Jianbo Sun*
Affiliation:
- Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009,China
- Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009,China
Keywords:
Furo[2, 3-b]quinolone, breast cancer, design and synthesis, cytotoxic activity, topoisomerase II, MTT.
Abstract: A number of novel furo[2,3-b]quinoline derivatives were designed and synthesized by introducing
different substituted anilines and phenols to C4-position of furo[2,3-b]quinoline. All target compounds were
evaluated in vitro against two human breast cancer cell lines (MCF-7 and MDA-MB-231) and one normal breast
cell (MCF-10A) by MTT (3-[4,5-dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium broide, Thiazolyl blue)
method. Most derivatives showed significant cytotoxic activity on the two breast cancer cells with IC50 values in
the range of (5.60-26.24 μM) and a certain selectivity, especially in the inhibition of MDA-MB-231. More
notably, they were less toxic to normal breast cell (MCF-7-10A). Compound I7 could be considered as an ideal
selective candidate for further study. Mechanism studies showed that I7 could inhibit the proliferation of cells by
arresting MDA-MB-231 cell cycle at G2/M phase. Overall, as a novel furo[2,3-b]quinoline derivative, I7
exhibited an excellent inhibitory effect in MDA-MB-231 cell and was worthy of in-depth study.