Does hydrophobicity always enhance antioxidant drugs? A cut-off effect of the chain length of functionalized chlorogenate esters on ROS-overexpressing fibroblasts - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Journal of Pharmacy and Pharmacology Year : 2011

Does hydrophobicity always enhance antioxidant drugs? A cut-off effect of the chain length of functionalized chlorogenate esters on ROS-overexpressing fibroblasts

Abstract

Objectives: Phenolic antioxidants are currently attracting a growing interest as potential therapeutic agents to counteract diseases associated with oxidative stress. However, their high hydrophilicity results in a poor bioavailability hindering the development of efficient antioxidant strategies. A promising way to overcome this is to increase their hydrophobicity by lipophilic moiety grafting to form the newly coined ‘phenolipids’. Although hydrophobicity is generally considered as advantageous regarding antioxidant properties, it is nevertheless worth investigating whether increasing hydrophobicity necessarily leads to a more efficient antioxidant drug. Methods: To answer this question, the antioxidant capacity of a homologous series of phenolics (chlorogenic acid and its methyl, butyl, octyl, dodecyl and hexadecyl esters) toward mitochondrial reactive oxygen species (ROS) generated in a ROS-overexpressing fibroblast cell line was investigated using 2′,7′-dichlorodihydrofluorescein. Key findings Overall, the long chain esters (dodecyl and hexadecyl esters) were more active than the short ones (methyl, butyl, and octyl esters), with an optimal activity for dodecyl chlorogenate. Moreover, dodecyl chlorogenate exerted a strong antioxidant capacity, for concentration and incubation time below the cytotoxicity threshold, making it a promising candidate for further in-vivo studies. More importantly, we found that the elongation of the chain length from 12 to 16 carbons led unexpectedly to a 45% decrease of antioxidant capacity. Conclusion: The understanding of this sudden collapse of the antioxidant capacity through the cut-off theory will be discussed in this article, and may contribute towards development of a rational approach to design novel amphiphilic antioxidant drugs, especially phenolipids with medium fatty chain.

Dates and versions

hal-02648848 , version 1 (29-05-2020)

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Mickaël Laguerre, Chantal Wrutniak Cabello, Béatrice Chabi, Luis J. López Giraldo, Jérôme J. Lecomte, et al.. Does hydrophobicity always enhance antioxidant drugs? A cut-off effect of the chain length of functionalized chlorogenate esters on ROS-overexpressing fibroblasts. Journal of Pharmacy and Pharmacology, 2011, 63 (4), pp.531-540. ⟨10.1111/j.2042-7158.2010.01216.x⟩. ⟨hal-02648848⟩
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