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

doi:10.6023/cjoc202001021

Chinese Journal of Organic Chemistry ›› 2020, Vol. 40 ›› Issue (8): 2374-2386.DOI: 10.6023/cjoc202001021 Previous Articles Next Articles

樟脑基缩氨基硫脲衍生物通过活性氧(ROS)介导的线粒体途径诱导人乳腺癌细胞的G2期阻滞和凋亡

张燕^a, 王芸芸^a, 赵雨珣^a, 张成龙^a, 谷文^a, 王忠龙^a, 朱永强^b, 王石发^a

a 南京林业大学化学工程学院南京林业大学林业资源高效加工利用协同创新中心南京 210037;
b 江苏正大丰海制药有限公司南京 210033

收稿日期:2020-01-14 修回日期:2020-05-22 发布日期:2020-06-10
通讯作者: 王石发, 朱永强 E-mail:wangshifa65@163.com;zhyqscu@163.com
基金资助:
南京林业大学博士研究生基金会、国家自然科学基金（No.31470592）、江苏省高校自然科学研究重大项目（No.14KJ220001）和油性树脂的绿色加工及高效利用的关键技术（No.2016YFD0600804）资助项目.

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^a, Wang Yunyun^a, Zhao Yuxun^a, Zhang Chenglong^a, Gu Wen^a, Wang Zhonglong^a, Zhu Yongqiang^b, Wang Shifa^a

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:2020-01-14 Revised:2020-05-22 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).

1. cjoc202001021.pdf(3221KB)

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.

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樟脑基缩氨基硫脲衍生物通过活性氧(ROS)介导的线粒体途径诱导人乳腺癌细胞的G2期阻滞和凋亡

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

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