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

作　　者：Xinlu Chai Yuting Meng Wei Ge Juan Wang Fei Li Xue Jun Wang Xuerong Wang 

机构地区：[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.

出　　处：《The Journal of Biomedical Research》2023年第5期355-366,共12页生物医学研究杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.81972763 and 81473241).

摘　　要：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.

关 键 词：GEMCITABINE THIAZOLIDINONE H2O2-sensitive moiety non-small cell lung cancer 

分 类 号：R966[医药卫生—药理学]