Development of Furo[2,3-b]quinoline Derivatives with Anti-Breast Cancer Property by Targeting Topoisomerase II

Author(s):

Ying Wang, Na Li, Neng Jiang, Li Chen* and Jianbo Sun*   Pages 1482 - 1489 ( 8 )

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.

Keywords:

Furo[2,3-b]quinolone, breast cancer, design and synthesis, cytotoxic activity, topoisomerase II, MTT.

Affiliation:

Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, Department of Clinical Pharmacy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009

Graphical Abstract:

Read Full-Text article