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, 2023, 37(5): 355-366. DOI: 10.7555/JBR.37.20230022 |
In the present 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. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could 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 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.
This work was supported by the National Natural Science Foundation of China (Grant Nos. 81972763 and 81473241).
We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.
CLC number: R966, Document code: A
The authors reported no conflict of interests.
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