A potential prodrug for a green tea polyphenol proteasome inhibitor: evaluation of the peracetate ester of (−)-epigallocatechin gallate [(−)-EGCG]
| Autor: | Deborah J. Kuhn, Albert S. C. Chan, Larry M.C. Chow, Aslamuzzaman Kazi, Wai Har Lam, Q. Ping Dou, Tak Hang Chan |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Proteasome Endopeptidase Complex
Clinical Biochemistry Flavonoid Drug Evaluation Preclinical Pharmaceutical Science Epigallocatechin gallate complex mixtures Biochemistry Catechin Jurkat Cells chemistry.chemical_compound Phenols Drug Discovery medicine Humans Prodrugs Protease Inhibitors heterocyclic compounds Peracetic Acid Molecular Biology Flavonoids chemistry.chemical_classification Tea biology Organic Chemistry Polyphenols food and beverages Esters Biological activity Prodrug chemistry Enzyme inhibitor Polyphenol biology.protein Proteasome inhibitor Molecular Medicine sense organs Proteasome Inhibitors medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry. 12:5587-5593 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2004.08.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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