Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation.

Cristina Minnelli,Dario Rusciano,Emiliano Laudadio,Pierluigi Stipa,Adolfo Amici,Giovanna Mobbili,Tatiana Armeni,Roberta Galeazzi,Mattia Cantarini

doi:10.3390/antiox9030208

Cristina Minnelli, Dario Rusciano + Show 7 more

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https://doi.org/10.3390/antiox9030208

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Journal: Antioxidants	Publication Date: Mar 3, 2020
Citations: 32	License type: CC BY 4.0

Affiliation: Marche Polytechnic University

Abstract

Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial effects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application in lipophilic media, in particular the cellular absorption. At this purpose the hydrophilic EGCG was modified by inserting an aliphatic C18 chain linked to the gallate ring by an ethereal bond, the structure determined by NMR (Nuclear Magnetic Resonance) and confirmed by Density Functional Theory (DFT) calculations. The in vitro antioxidant activity of the mono-alkylated EGCG (C18-EGCG) was studied by the DPPH and Thiobarbituric Acid Reactive Substances (TBARS) assays, and its ability to protect cells towards oxidative stress was evaluated in Adult Retinal Pigmented Epithelium (ARPE-19) cells. Molecular Dynamics (MD) simulation and liposomal/buffer partition were used to study the interaction of the modified and unmodified antioxidants with a cell membrane model: the combined experimental-in silico approach shed light on the higher affinity of C18-EGCG toward lipid bilayer. Although the DPPH assay stated that the functionalization decreases the EGCG activity against free radicals, from cellular experiments it resulted that the lipid moiety increases the antioxidant protection of the new lipophilic derivative.

Highlights

Epigallocatechin-3-gallate (EGCG), a polyphenolic catechin from green tea, is a well-known molecule active in age-related illnesses where oxidative stress plays a key role, including cataract, Dry Eye Syndrome (DES) and Age-Related Macular Degeneration (AMD) [1,2,3]
With the aim to obtaini a more lipophilic EGCG derivative with an improved affinity for a lipid bilayer and other oxidation-susceptible cellular sites, the molecular skeleton of the natural antioxidant
EGCG was modified by the introduction of a C-18 hydrocarbon chain; such an aliphatic tail has been bound by an ether linkage employing the Williamson reaction (Scheme 2) and the structure of the main mono-alkylated product has been confirmed by nuclear magnetic resonance (NMR) specroscopy and mass spectrometry

Summary

Introduction

Epigallocatechin-3-gallate (EGCG), a polyphenolic catechin from green tea, is a well-known molecule active in age-related illnesses where oxidative stress plays a key role, including cataract, Dry Eye Syndrome (DES) and Age-Related Macular Degeneration (AMD) [1,2,3]. The EGCG structure presents a benzenediol ring (label A) joined to a tetrahydropyran moiety (C), a pyrogallol ring (B) and a galloyl ring (D) (Figure 1). Antioxidants 2020, 9, 208; doi:10.3390/antiox9030208 www.mdpi.com/journal/antioxidants Antioxidants. Antioxidants 2020, 9, x FOR PEER REVIEW Figure 1. Structure of of epigallocatechin-3-gallate, epigallocatechin-3-gallate, aa green green tea tea polyphenol. Multiple mechanisms contribute toto the overall antioxidant effect: radical scavenging activity [4,5], Multiple

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