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

In the present study, we introduced the H 2O 2-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. We further confirmed that GEM-ZZQ had...

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Published in:Journal of biomedical research 2023-09, Vol.37 (5), p.355-366
Main Authors: Chai, Xinlu, Meng, Yuting, Ge, Wei, Wang, Juan, Li, Fei, Wang, Xue Jun, Wang, Xuerong
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container_end_page 366
container_issue 5
container_start_page 355
container_title Journal of biomedical research
container_volume 37
creator Chai, Xinlu
Meng, Yuting
Ge, Wei
Wang, Juan
Li, Fei
Wang, Xue Jun
Wang, Xuerong
description In the present study, we introduced the H 2O 2-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. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H 2O 2 to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment 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 the GEM structure.
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title A novel synthesized prodrug of gemcitabine based on oxygen-free radical sensitivity inhibited the growth of lung cancer cells
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