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Synthesis and antitumor properties of novel alizarin analogs

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Abstract

Series of novel hybrids of alizarin and diamide scaffold (3a–3h, 7a–7h) were designed and synthesized. In vitro antitumor activities of all compounds against HepG-2, CNE, Spca-2, Hct-116, and MGC-803 cell lines were evaluated, and employing standard MTT assay compared with commercial anticancer drug 5-fluorouracil (5-FU). Compounds 7b, 7c, 7d, and 7e showed relatively high cytotoxicity. Especially, compound 7c exhibited the best cytotoxicity against CNE cells with IC50 9.08 µM, which was even stronger than that of 5-FU. All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The action mechanism of representative compound 7c was preliminarily investigated by flow cytometry, which indicated that the compound can induce cell apoptosis in CNE cells. Cell cycle analysis showed that compound 7c mainly arrested CNE cells in G1 stage. In addition, the binding properties of a model analog 7c to DNA were investigated by different methods (fluorescence, CD spectroscopy), and the results indicated that 7c showed a moderate preference for binding ct-DNA.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Nos. 81260472, 21101035, and 21362002), Guangxi Natural Science Foundation of China (Nos. 2011GXNSFD018010 and 12118008-10), Bagui Scholar project, and the Foundation of Ministry of Education Innovation Team (No. IRT1225).

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, People’s Republic of China

    Guiyang Yao & Zhi-Xin Liao

  2. State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Sciences of Guangxi Normal University, Guilin, 541004, People’s Republic of China

    Weilong Dai, Manyi Ye, Rizhen Huang, Ying-ming Pan & Heng-shan Wang

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  1. Guiyang Yao
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  2. Weilong Dai
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  3. Manyi Ye
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  4. Rizhen Huang
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  5. Ying-ming Pan
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  6. Zhi-Xin Liao
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  7. Heng-shan Wang
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Correspondence to Zhi-Xin Liao or Heng-shan Wang.

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Yao, G., Dai, W., Ye, M. et al. Synthesis and antitumor properties of novel alizarin analogs. Med Chem Res 23, 5031–5042 (2014). https://doi.org/10.1007/s00044-014-1062-5

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  • DOI: https://doi.org/10.1007/s00044-014-1062-5

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