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Comparison of a Pair of Synthetic Tea-Catechin-Derived Epimers: Synthesis, Antifolate Activity, and Tyrosinase-Mediated Activation in Melanoma
Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin‐derived compounds, 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐catechin (TMCG) and 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐epicatechin (TMECG...
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Published in: | ChemMedChem 2011-03, Vol.6 (3), p.440-449 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Despite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin‐derived compounds, 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐catechin (TMCG) and 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐epicatechin (TMECG), in an attempt to improve the stability and cellular absorption of tea polyphenols. The antiproliferative and pro‐apoptotic activities of both compounds were analyzed with various cancer cell systems, and TMCG, which was easily synthesized in excellent yield, was more active than TMECG in both melanoma and non‐melanoma cell lines. TMCG was also a better inhibitor of dihydrofolate reductase and was more efficiently oxidized by tyrosinase, potentially explaining the difference in activity between these epimers.
One small but important difference: Herein we report the synthesis and biological evaluation of two epimeric compounds derived from the structure of tea catechins. The catechin epimer was more effective than the epicatechin epimer as an antitumor drug against various cancer cell systems. These epimeric differences could be due to greater inhibition of dihydrofolate reductase by the catechin derivative and more efficient oxidation of this derivative by tyrosinase in melanoma cells. |
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ISSN: | 1860-7179 1860-7187 |
DOI: | 10.1002/cmdc.201000482 |