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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 8: 2374 - 2386

DOI: https://doi.org/10.6023/cjoc202001021

Camphor-Based Thiosemicarbazone Analogues Induced G2 Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species (ROS)-Mediated Mitochondrial Pathway in Human Breast Cancer Cells

  • Zhang Yan ,
  • Wang Yunyun ,
  • Zhao Yuxun ,
  • Zhang Chenglong ,
  • Gu Wen ,
  • Wang Zhonglong ,
  • Zhu Yongqiang ,
  • Wang Shifa
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  • a Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037;
    b Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd, Nanjing 210033

Received date: 2020-01-14

  Revised date: 2020-05-22

  Online published: 2020-06-10

Supported by

Project supported by the Doctorate Fellowship Foundation of Nanjing Forestry University, the Natural National Science Foundation of China (No. 31470592), the University Science Research Project of Jiangsu Province (No. 14KJ220001) and the Key Technology of Green Processing and Efficient Utilization on Oleoresin (No. 2016YFD0600804).

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Abstract

22 novel camphor-based thiosemicarbazone derivatives were synthesized using camphor-based thiosemicarbazone as material and their structures were determined by 1H NMR, 13C NMR and HRMS. The crystal structure of 2-(3-(pyridin-4-ylmethylene)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarbothioamide (3n) was determined by single crystal X-ray diffraction. The derivatives were screened in vitro for anticancer activities against human breast cancer cell line (MDA-MB-231), human lung adenocarcinoma cell line (A549), human multiple myeloma cell line (RPMI-8226) and toxicity against a normal human cell line (GES-1) by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). It was found that majority of the tested analogs showed moderate to significant antitumor activity against selected cancer cell lines. Noticeably, 2-(3-(anthracen-9-ylmethylene)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)-hydrazinecarbothioamide (3s) exhibited selective anti-tumor activities against MDA-MB-231 cells (IC50=3.90±0.04 μmol·L-1) and low toxicity to GES-1 cells (IC50>50 μmol·L-1). In the process of exploring the underlying mechanism of 3s, it was found that compound 3s could cause G2 phase arrest and apoptosis in MDA-MB-231 cells by overproduction of intracellular reactive oxygen species and collapse of mitochondrial membrane potential. The measured results were confirmed by western blot assay.

Key words： camphor-based thiosemicarbazone; anti-tumor activity; G2 phase arrest; reactive oxygen species (ROS); mitochondrial apoptosis pathway

Cite this article

Zhang Yan , Wang Yunyun , Zhao Yuxun , Zhang Chenglong , Gu Wen , Wang Zhonglong , Zhu Yongqiang , Wang Shifa . Camphor-Based Thiosemicarbazone Analogues Induced G2 Cell Cycle Arrest and Apoptosis via Reactive Oxygen Species (ROS)-Mediated Mitochondrial Pathway in Human Breast Cancer Cells[J]. Chinese Journal of Organic Chemistry, 2020 , 40(8) : 2374 -2386 . DOI: 10.6023/cjoc202001021

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