| Abstract: | Eighteen novel 2,3‐diphenyl acrylonitrile derivatives bearing halogens were designed, synthesized, and evaluated for biological activity. Preliminary in vitro results indicated that the majority of the compounds with a para‐substituted halogen had considerable antiproliferative activity against five human cancer cell lines, including MGC‐803, AGS, and BEL‐7402, with IC50 values in the range of 0.46–100 μm . No significant toxic effects on the non‐cancerous human liver cell line L‐02 were observed. The selective inhibitory activities against cancer cells were significantly better than that of the control lead compound CA‐4 and CA‐4P. Particularly, potent activities were found for the derivatives of 3‐(4‐halogen phenyl)‐2‐(3,4,5‐trimethoxyphenyl)acrylonitrile, such as 5c (4‐fluoro), 5f (4‐bromo), 5h (4‐chloro), and 5k (4‐trifluoro‐ methyl), for AGS with IC50 values of 0.75 ± 0.24, 0.68 ± 0.21, 0.41 ± 0.05, and 1.49 ± 0.92 μm , respectively. The antiproliferative effects of 5f were attributed to cell‐cycle arrest in the G2/M phase, induction of cellular apoptosis, suppression of cell migration, and inhibition of cell colony formation in AGS cells. |
