Structure-based design, structure-activity relationship analysis, and antitumor activity of diaryl ether derivatives.
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.
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Shao-Mei
SM
Yang
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Zhi-Ning
ZN
Huang
Department of Basic Medical Sciences of Medical College, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Zhong-Shi
ZS
Zhou
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Jin
J
Hou
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Man-Yi
MY
Zheng
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Li-Juan
LJ
Wang
Department of Outpatient, Air Force of Chengdu Military Command, 87 New South Road, Chengdu, 610041, People's Republic of China.
Yu
Y
Jiang
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Xin-Yi
XY
Zhou
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Qiu-Yue
QY
Chen
Department of Basic Medical Sciences of Medical College, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China.
Shan-Hua
SH
Li
School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, 361102, People's Republic of China. fnlee5@xmu.edu.cn.
Fu-Nan
FN
Li
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004987:Ethers; D053148:Caspase 3
Antitumor; Diaryl ethers; Structural modification