2. Academic Validation
  3. Synthesis and biological evaluation of novel alkylated polyamine analogues as potential anticancer agents

Synthesis and biological evaluation of novel alkylated polyamine analogues as potential anticancer agents

  • Eur J Med Chem. 2018 Jan 1:143:1732-1743. doi: 10.1016/j.ejmech.2017.10.069.
Meng Li 1,  Yuxia Wang 2,  Chaochao Ge 3,  Liping Chang 3,  Chaojie Wang 3,  Zhiyong Tian 4,  Senzhen Wang 3,  Fujun Dai 5,  Luyao Zhao 1,  Songqiang Xie 6
Affiliations

Affiliations

  • 1 Pharmaceutical College, Henan University, Kaifeng 475004, Henan, China.
  • 2 College of Chemistry and Chemical Engineering, Henan University, Kaifeng 475004, Henan, China.
  • 3 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan, China.
  • 4 Pharmaceutical College, Henan University, Kaifeng 475004, Henan, China. Electronic address: tzynew@163.com.
  • 5 Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, Kaifeng 475004, Henan, China. Electronic address: fjdwl@vip.henu.edu.cn.
  • 6 Pharmaceutical College, Henan University, Kaifeng 475004, Henan, China. Electronic address: xiesq@henu.edu.cn.
PMID: 29133040 DOI: 10.1016/j.ejmech.2017.10.069
Abstract

A new class of polyamine analogues modified by alkylation at the terminal of the polyamine chain has been synthesized and their structures were determined by 1H NMR, 13C NMR, ESI-MS and elemental analysis. As the representative compound, 3f displayed a broad spectrum of anti-cancer effects by MTT assays. Tumor xenograft model and pulmonary metastasis model showed that compound 3f significantly suppressed tumor growth and metastasis in vivo, which was more stronger than the reference drug amonafide. Molecular mechanisms indicated that compound 3f exhibited antiproliferative activities and induced the generation of Reactive Oxygen Species (ROS), which resulted in the occurrence of Autophagy. The downregulated expression of MMP-9 and β-catenin by compound 3f accounted for the inhibition of migration. Taken altogether, the in vitro and in vivo biological evaluations corroborated compound 3f to be an effective Anticancer agent.

Keywords

Autophagy; Cancer; Polyamine; ROS.

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