Synthesis and Pharmacological Evaluation of 2,3-Diphenyl Acrylonitrile Bearing Halogen as Selective Anticancer Agents

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 anti-proliferatory 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 antiproliferation 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.

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Eighteen novel 2,3-diphenyl acrylonitrile derivatives-bearing halogens were synthesized. The majority of the compounds with a para-substituted halogen had considerable selective anticancer activity in vitro with no toxic effects on L-02 normal liver cells. The selective inhibitory activities against cancer cells were significantly better than that of the control lead compound CA-4 and CA-4P. Among them, the antiproliferation effects of 3-(4-bromophenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (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.

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