A potential prodrug for a green tea polyphenol proteasome inhibitor: Evaluation of the peracetate ester of (-)-epigallocatechin gallate [(-)-EGCG]

Wai Har Lam, Aslamuzzaman Kazi, Deborah J. Kuhn, Ming Cheung Chow, Albert S C Chan, Q. Ping Dou, Tak Hang Chan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

105 Citations (Scopus)


Green tea has been shown to have many biological effects, including effects on metabolism, angiogenesis, oxidation, and cell proliferation. Unfortunately, the most abundant green tea polyphenol (-)-epigallocatechin gallate or (-)-EGCG is very unstable in neutral or alkaline medium. This instability leads to a low bioavailability. In an attempt to enhance the stability of (-)-EGCG, we introduced peracetate protection groups on the reactive hydroxyls of (-)-EGCG (noted in text as 1). HPLC analysis shows that the protected (-)-EGCG analog is six times more stable than natural (-)-EGCG under slightly alkaline conditions. A series of bioassays show that 1 has no inhibitory activity against a purified 20S proteasome in vitro, but exhibits increased proteasome-inhibitory activity in intact leukemic cells over natural (-)-EGCG, indicating an intercellular conversion. Inhibition of cellular proteasome activity by 1 is associated with induction of cell death. Therefore, our results indicate that the protected analog 1 may function as a prodrug of the green tea polyphenol proteasome inhibitor (-)-EGCG.
Original languageEnglish
Pages (from-to)5587-5593
Number of pages7
JournalBioorganic and Medicinal Chemistry
Issue number21
Publication statusPublished - 1 Nov 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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