ABSTRACT
Analogs of (-)-EGCG containing a para-amino group on the D-ring in place of the hydroxyl groups have been synthesized and their proteasome inhibitory activities were studied. We found that, the O-acetylated (-)-EGCG analogs possessing a p-NH(2) or p-NHBoc (Boc; tert-butoxycarbonyl) D-ring (5 and 7) act as novel tumor cellular proteasome inhibitors and apoptosis inducers with potency similar to natural (-)-EGCG and similar to (-)-EGCG peracetate. These data suggest that the acetylated amino-GTP analogs have the potential to be developed into novel anticancer agents.
Subject(s)
Catechin/analogs & derivatives , Tea/chemistry , Apoptosis/drug effects , B-Lymphocytes/drug effects , Caspase 3/metabolism , Catechin/chemistry , Catechin/pharmacology , Cell Line, Tumor , Humans , Leukemia/drug therapy , Molecular Structure , Proteasome Endopeptidase Complex/metabolism , Structure-Activity RelationshipABSTRACT
The total and semi syntheses of (2R, 3R)-epigallocatechin-3-O-(4-hydroxybenzoate), a novel catechin from Cistus salvifolius, was accomplished. The proteasome inhibition and cytotoxic activities of the synthetic compound and its acetyl derivative were studied and compared with (2R, 3R)-epigallocatechin-3-gallate (EGCG), the active component from green tea.
