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

93 Citations (Scopus)

Abstract

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
Volume12
Issue number21
DOIs
Publication statusPublished - 1 Nov 2004

ASJC Scopus subject areas

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

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