Prodrugs of Fluoro-Substituted Benzoates of EGC as Tumor Cellular Proteasome Inhibitors and Apoptosis Inducers

International Journal of Molecular Sciences

Zhiyong Yu²  Xu Long Qin²  Yan Yan Gu¹  Di Chen²  Qiuzhi Cindy Cui²  Tao Jiang¹  Sheng Biao Wan¹ 

[1] Key Laboratory of Marine Drug, Ministry of Education, Medical College, Ocean University of China, Qingdao, China;The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan, USA

关键词: tea polyphenols;    prodrugs;    proteasome inhibitors;    cancer prevention;    cancer therapy;   

DOI  :  10.3390/ijms9060951

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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