A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells

Xinlu Chai; Yuting Meng; Wei Ge; Juan Wang; Fei Li; Xue Jun Wang; Xuerong Wang

doi:10.7555/JBR.37.20230022

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Xinlu Chai, Yuting Meng, Wei Ge, Juan Wang, Fei Li, Xue Jun Wang, Xuerong Wang. A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.37.20230022

Citation:

Xinlu Chai, Yuting Meng, Wei Ge, Juan Wang, Fei Li, Xue Jun Wang, Xuerong Wang. A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.37.20230022

Citation:

Xinlu Chai, Yuting Meng, Wei Ge, Juan Wang, Fei Li, Xue Jun Wang, Xuerong Wang. A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells[J]. The Journal of Biomedical Research. doi: 10.7555/JBR.37.20230022

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A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells

doi: 10.7555/JBR.37.20230022

Xinlu Chai^{1, △},
Yuting Meng^{1, △},
Wei Ge¹,
Juan Wang²,
Fei Li³,
Xue Jun Wang^{4
,
,},
Xuerong Wang^{1
,
,}

1.
Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, China
2.
Department of Pharmacology, Wannan Medical College, Wuhu, Anhui 241002, China
3.
Department of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 210029, China
4.
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210029, China

More Information

Corresponding author: Xue Jun Wang, Department of Biochemistry and Molecular Biology, Nanjing Medical University, 101 Longmian Boulevard, Nanjing, Jiangsu, 210029, China. Tel/Fax: 025-86869322, Email: wangxuejun@njmu.edu.cn; Xuerong Wang, Department of Pharmacology, Nanjing Medical University, 101 Longmian Boulevard, Nanjing, Jiangsu, 210029, China. Tel/Fax: 025-868689406, Email: wangxr@njmu.edu.cn
Received: 2023-02-03
Revised: 2023-04-28
Accepted: 2023-05-05

Published: 2023-05-28

Abstract

Abstract

In the current study, we introduced the H₂O₂-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine (GEM) to synthesize a new target compound named GEM-ZZQ, and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy. It was further confirmed that GEM-ZZQ has a good chemical stability in different pH solutions in vitro and that it can be activated by H₂O₂ to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM. For the lung cancer cell lines that are resistant to the epidermal growth factor receptor (EGFR)-targeting inhibitor osimertinib, GEM-ZZQ showed less growth inhibition than GEM; however, GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups. In summary, we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying GEM structure.
- gemcitabine,
- thiazolidinone,
- H₂O₂-sensitive moiety,
- non-small cell lung cancer

CLC number: R966, Document code: A
The authors reported no conflict of interests.
△These authors contributed equally to this work.

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References(29)

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