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.
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This work was supported by the National Natural Science Foundation of China (NSFC-81472230), and the Fundamental Research Funds for the Xiamen Universities (CXB-2014011).
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Shao-Mei Yang and Zhi-Ning Huang have contributed equally to this work.
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Yang, SM., Huang, ZN., Zhou, ZS. et al. Structure-based design, structure–activity relationship analysis, and antitumor activity of diaryl ether derivatives. Arch. Pharm. Res. 38, 1761–1773 (2015). https://doi.org/10.1007/s12272-015-0578-7
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DOI: https://doi.org/10.1007/s12272-015-0578-7