Synthesis, cytotoxicity and pro-apoptosis of novel benzoisoindolin hydrazones as anticancer agent

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  • Zhao Yu
    Institute of Nautical Medicine, Nantong University
  • Hui Jie
    Institute of Nautical Medicine, Nantong University
  • Wang Dan
    Institute of Nautical Medicine, Nantong University
  • Zhu Li
    Institute of Nautical Medicine, Nantong University
  • Fang Jing-Huai
    School of Science, Nantong University
  • Zhao Xiao-Dong
    School of Electromechanical Engineering, Zhejiang Ocean University

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  • Synthesis, Cytotoxicity and Pro-apoptosis of Novel Benzoisoindolin Hydrazones as Anticancer Agents

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A series of benzoisoindolin hydrazones as analogues of natural lignan diphyllin were synthesized and the structures of these compounds were established by 1H-NMR, 13C-NMR, Mass and high resolution (HR)-MS. The compounds were evaluated for in vitro cytotoxicity against KB, A549 and HCT-116 cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compound 4 possessed the highest growth inhibitory effect. Significant apoptosis of HCT-116 cells treated with compound 4 was observed by Hoechst33342-propidium iodide (PI) and acridine orange (AO)-ethidium bromide (EB) staining assay. Western blot analysis disclosed that compound 4 induced apoptosis via the mitochondrial pathway accompanied by an increased expression of Bax and a decreased expression of Bcl-2.

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