Catechin prodrugs and analogs: a new array of chemical entities with improved pharmacological and pharmacokinetic properties

Abstract

Extensive research on tea catechins, mainly (-)-epigallocatechin gallate, has shown numerous health promoting effects. However, various clinical studies demonstrated several issues associated with tea catechins which account for their poor systemic bioavailability. In order to improve pharmacological activity and bioavailability of natural tea catechins, two major strategies have been adopted to date which include synthesizing catechin analogs/prodrugs and the development of novel drug delivery systems. In this review, we provide a detailed account of novel synthetic analogs/prodrugs as well as novel drug delivery approaches used for natural tea catechins to make them therapeutically potent drug-like molecules.

Topical (+)-catechin emulsified gel prevents DMBA/TPA-induced squamous cell carcinoma of the skin by modulating antioxidants and inflammatory biomarkers in BALB/c mice

“…31 In addition, these natural antioxidants possess the ability to detoxify enzyme components, such as GST. 15 The current reports further verify that the bioavailability issue of these compounds can be overcome by delivering these compounds via a topical route of drug administration. 15 The current reports further verify that the bioavailability issue of these compounds can be overcome by delivering these compounds via a topical route of drug administration.…”

“…4 These polyphenols have been found to exert antioxidant, 5,6 anticancer, 7,8 antiviral, 9,10 antibacterial, 11,12 and anti-inflammatory 13,14 actions in both in vitro and in vivo models. 15 In our previous research, we found that a (+)-catechin rich aqueous extract of Acacia catechu shows chemopreventive effects against skin, 16 liver, 17 and breast cancers. 1).…”

“…The (+)-catechin is widely distributed in various plants like Camellia sinensis (tea) and Acacia catechu Willd. 15 The topical delivery of polyphenols is an attractive approach to bypass the first-pass metabolism and at the same time, it can be directly applied to the area of interest. 18 At the same time, we reported the growth inhibition and apoptosis induction potential of (+)-catechin against hepatocellular 19 and breast carcinoma.…”

An Amide Analog of (−)‐Epigallocatechin Gallate Shows Preferential Cytotoxicity toward Triple‐Negative Breast Cancer Cells

“…From a synthetic point of view, replacement of the bridging ester with other functionalities is more challenging than substitution at the peripheral phenolic hydroxyl groups (OR, Figure ). In addition, substitution at the epimerization‐susceptible 3‐position provides additional consideration . In this study, we devised a synthetic route to an amide analog of EGCG [EGCG‐Amide ( 3 ), Figure ], which showed preferential cytotoxicity toward triple‐negative breast cancer cell.…”

Synthesis of diverse catechin congeners via diastereoselective intramolecular epoxy-arene cyclization

“…3 Not surprisingly, there have been significant activities toward the synthesis of these molecules and their derivatives to explore and improve the biological profiles. 4 A common feature of catechins is that they undergo oxidative oligomerization in vivo through the benzylic position of the C-ring and hence potential bioaccessibility of parent catechins is reduced. 3 Along this line, we hypothesize that with the congeneric 4-arylchroman-3-ols ( Figure 1) the relevant biological activities might not be compromised 5 and oxidative oligomerization might be suppressed.…”