An NAD(P)H:Quinone Oxidoreductase 1 Responsive and Self-Immolative Prodrug of 5-Fluorouracil for Safe and Effective Cancer Therapy

作者：Zhang, Xian; Li, Xiang; Li, Zhihong; Wu, Xingsen; Wu, Yue; You, Qidong^*; Zhang, Xiaojin^*

来源：Organic Letters, 2018, 20(12): 3635-3638.

DOI：10.1021/acs.orglett.8b01409

• CELL LUNG-CANCER
• OVEREXPRESS NQO1
• BETA-LAPACHONE
• QUINONE
• REDUCTASE
• DISCOVERY

Tripartite prodrug 1, composed of an NAD(P)-H:quinone oxidoreductase 1 (NQO1)-responsive trigger group, a self-immolative linker, and the active drug 5-fluorouracil (5-FU), was designed and synthesized for site-specific cancer therapy. Upon bioreductive activation by NQO1, 1 can release the parent drug 5-FU specifically in NQO1-overexpressing cancer cells. This prodrug exerts comparable antitumor activity and a more favorable safety profile compared with 5-FU both in vitro and in vivo.

• 出版日期2018-6-15
• 单位中国药科大学