Prodrugs of fluoro-substituted benzoates of EGC as tumor cellular proteasome inhibitors and apoptosis inducers.
The most potent catechin in green tea is (-)-epigallocatechin-3-gallate [(-)-EGCG], which, however, is unstable under physiological conditions. To discover more stable and more potent polyphenol proteasome inhibitors, we synthesized several novel fluoro-substituted (-)-EGCG analogs, named F-EGCG analogs, as well as their prodrug forms with all of -OH groups protected by acetate. We report that the prodrug form of one F-EGCG analog exhibited greater potency than the previously reported peracetate of (-)-EGCG to inhibit proteasomal activity, suppress cell proliferation, and induce apoptosis in human leukemia Jurkat T cells, demonstrating the potential of these compounds to be developed into novel anti-cancer and cancer-preventive agents.
Yu
Zhiyong
Z
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA.|Shandong Tumor Hospital & Institute, Breast Cancer Center, Jinan, Shandong, China.
Qin
Xu Long
XL
Key Laboratory of Marine Drug, Ministry of Education, Medical College, Ocean University of China, Qingdao, China..
Gu
Yan Yan
YY
Key Laboratory of Marine Drug, Ministry of Education, Medical College, Ocean University of China, Qingdao, China..
Chen
Di
D
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA.
Cui
Qiuzhi Cindy
QC
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA.
Jiang
Tao
T
Key Laboratory of Marine Drug, Ministry of Education, Medical College, Ocean University of China, Qingdao, China..
Wan
Sheng Biao
SB
Key Laboratory of Marine Drug, Ministry of Education, Medical College, Ocean University of China, Qingdao, China..
Dou
Q Ping
QP
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA.