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Synthesis and antitumor activity of a new 7-azaindole derivative

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Abstract

We designed and synthesized a 7-azaindole derivative(TH1082), which was characterized by 1H NMR and 13C-NMR. We investigated its antitumor effects on human melanoma A375 cells, human liver cancer SMMC cells and human breast cancer MCF-7 cells in vitro via 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and also explored the mechanism of antiproliferation of them. The results show that TH1082 significantly inhibited the proliferation of these cells to different extent. The IC50 values for A375 cells, SMMC cells and MCF-7 cells were 25.38, 48.70 and 76.94 μg/mL at 24 h, respectively. To observe cell morphological changes, acridine orange/ethidium bromide(AO/EB) staining and Hoechest33342/PI staining were carried out. These results indicate that TH1082 could induced the apoptosis of A375 cells. The apoptotic rates were (9.5±2.09)%, (18.9±2.25)% and (39.5±2.02)%(5, 10 and 20 μg/mL) for A375, SMMC and MCF-7 cell lines, respectively. Further, we determined the activities of caspase-3 and caspase-9 in A375 cells treated with TH1082 at different concentrations(0, 5, 10 and 20 μg/mL) or Z-VAD-FMK(20 μmol/L), a pan-caspase inhibitor for 24 h. The results show that TH1082 activated caspase-3 and caspase-9, and the activation could be blocked by Z-VAD-FMK. Taken together, these findings indicate that TH1082 could inhibit the proliferation of A375 cells via activating caspase-3 and caspase-9.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, P. R. China

    Peng Zhang, Dayun Sui, Huali Xu, Weilun Sun, Xiaofeng Yu, Shaochun Qu & Yi Wu

  2. Tianhe Pharmaceuticals Co., Ltd., Shenzhen, 518057, P. R. China

    Jianbing Hu & Yingshi Wang

Authors
  1. Peng Zhang
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  2. Dayun Sui
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  3. Huali Xu
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  4. Weilun Sun
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  5. Xiaofeng Yu
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  6. Shaochun Qu
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  7. Jianbing Hu
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  8. Yi Wu
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  9. Yingshi Wang
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Correspondence to Yi Wu or Yingshi Wang.

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Zhang, P., Sui, D., Xu, H. et al. Synthesis and antitumor activity of a new 7-azaindole derivative. Chem. Res. Chin. Univ. 30, 420–424 (2014). https://doi.org/10.1007/s40242-014-3468-5

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  • DOI: https://doi.org/10.1007/s40242-014-3468-5

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