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Synthesis, antitumor evaluation and molecular docking study of a novel podophyllotoxin-lonidamine hybrid

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Abstract

A novel podophyllotoxin-lonidamine hybrid was synthesized, and evaluated for its in vitro cytotoxicity by CCK-8 assay. The conjugate, Da, exhibited comparable antiproliferative activity in human normal and multidrug-resistance leukemia cancer cells. Flow cytometry suggested that Da could induce G2 phase cycle arrest and apoptosis of resistant K562/VCR cells, simultaneously increase the mitochondrial membrane depolarization. Furthermore, immunocytochemistry showed that Da could significantly disrupt the microtubule organization in K562/VCR cells. Molecular modeling demonstrated that Da was able to bind into the colchicine site of tubulin.

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Acknowledgements

This work was supported by the Department of Science and Technology of Guizhou Province (No. [2017]1219, [2014]7565, [2014]7557), Ministry of Education “Chunhui Project” Foundation of China (No. Z2015008), “Academic Youth & Innovation Exploration” of Zunyi Medical University and National First-Rate Construction Discipline of Guizhou Province (Pharmacy) (YLXKJS-YX-04).

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Authors and Affiliations

  1. Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563003, PR China

    Lei Zhang, Chengli Yang, Li Long, Yingshu Xu, Yongzheng Chen & Jing Wang

  2. Department of Nephrology and Rheumatology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, PR China

    Jie Zheng

  3. Second Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, PR China

    Ying Rong

  4. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China

    Qizheng Yao

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  1. Lei Zhang
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  2. Jie Zheng
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  3. Ying Rong
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  4. Chengli Yang
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  5. Li Long
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  6. Yingshu Xu
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  7. Yongzheng Chen
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  9. Qizheng Yao
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Correspondence to Lei Zhang or Jing Wang.

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Zhang, L., Zheng, J., Rong, Y. et al. Synthesis, antitumor evaluation and molecular docking study of a novel podophyllotoxin-lonidamine hybrid. Med Chem Res 27, 2231–2238 (2018). https://doi.org/10.1007/s00044-018-2230-9

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  • DOI: https://doi.org/10.1007/s00044-018-2230-9

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