Discovery of 3-phenylquinolinylchalcone derivatives as potent and selective anticancer agents against breast cancers

作者：Tseng Chih Hua; Tzeng Cherng Chyi; Hsu Chih Yao; Cheng Chih Mei; Yang Chia Ning; Chen Yeh Long^*

来源：European Journal of Medicinal Chemistry, 2015, 97: 306-319.

DOI：10.1016/j.ejmech.2015.04.054

• 3-Phenylquinolinylchalcone derivatives
• Anticancer agents
• Cell cycle
• Apoptosis
• Breast cancers

A number of 3-phenylquinolinylchalcone derivatives were synthesized and evaluated in vitro for their antiproliferative activities against three breast cancer cell lines (MCF-7, MDA-MB-231, and SKBR-3), and a non-cancer normal epithelial cell line (H184B5F5/M10). Among them, (E)-3-[3-(4-methoxyphenyl)quinolin-2-yl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (7) was active against the growth of MCF-7, MDA-MB-231, and SKBR-3 with IC50 values of 1.05, 0.75, and 0.78 mu M respectively without significant cytotoxicity to the normal H184B5F5/M10 cell line and therefore, was selected as a new lead for further mechanism studies. Results indicated that compound 7 inhibited the polymerization of tubulins, induced G2/M cell cycle arrest via modulation of the cyclin B1, cdk1 and CDC25. Compound 7 ultimately induced cell apoptosis by the increase of apoptotic protein Bax and the decrease of anti-apoptotic protein Bcl-2. In addition, PARP was cleaved while caspase-3 and -8 activities were induced after the treatment of compound 7 for 24 h in a concentration-dependent manner. Thus, compound 7 induces cell cycle arrest at G2/M phase via cleavage of PARP, induces caspase-3 and -8 activities and consequently to cause the cell death. Further study on the structure optimization of 7 is ongoing.

• 出版日期2015-6-5