Design, Synthesis, and Antitumor Activity of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones.

A series of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones (C1-C35) were designed and synthesized, and the structures of compounds (Z)-C27 and (Z)-C29 were confirmed by single-crystal X-ray diffraction. The antitumor activities of these novel compounds against cervical cancer (HeLa), lung cancer (A549), and breast cancer (MCF-7) cell lines were evaluated in vitro. Majority of the title compounds exhibited strong antitumor activities and were much more promising than the positive control Taxol, which were also accompanied by lower cytotoxicity to normal cells. In particular, compounds (E,Z)-C24 exhibited the most consistent potent activities against three neoplastic cells with IC50 values ranging from 3.2 to 7.1 μm. Further researches demonstrated that compounds (E,Z)-C24 could induce cell apoptosis and arrest cell cycle at the G2/M and S phases. Meanwhile, the structure-activity relationship between the configurations and cytotoxicity of the compounds was also investigated.