|
KMID : 0043320150380101761
|
|
Archives of Pharmacal Research
2015 Volume.38 No. 10 p.1761 ~ p.1773
|
|
|
Structure-based design, structure?activity relationship analysis, and antitumor activity of diaryl ether derivatives
|
|
Yang Shao Mei
Huang Zhi Ning
Zhou Zhong Shi
Hou Jin
Zheng Man Yi
Wang Li Juan
Jiang Yu
Zhou Xin Yi
Chen Qiu Yue
Li Shan Hua
Li Fu Nan
|
|
|
Abstract
|
|
|
|
To identify novel therapeutic agents to treat cancer, we synthesized a series of diaryl ether derivatives. Structure?activity relationship studies revealed that the presence of a chlorine or hydroxyl at the para-position on the phenyl ring (5h or 5k) significantly enhanced antitumor activity. Compound 5h had stronger growth inhibitory activity in HepG2, A549, and HT-29 cells than compound 5k, with IC50 values of 2.57, 5.48, and 30.04 μM, respectively. Compound 5h also inhibited the growth of other cells lines, including Hep3B, PLC/PRF5, SMMC-7721, HeLa, and A375, with IC50 values of 2.76, 4.26, 29.66, 18.86, and 10.21 μM, respectively. The antitumor activity of compound 5h was confirmed by a colony forming assay. Further, our results indicated that the antitumor activity of compound 5h may be mediated by enhancing expression of p21 and cl-caspase3, and leading to apoptosis of cancer cells.
|
|
|
KEYWORD
|
|
|
Diaryl ethers, Structural modification, Antitumor
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|
|