Interaction of wine anthocyanin derivatives with lipid bilayer membranes

Ossman, Tahani; Fabre, Gabin; Trouillas, Patrick

doi:10.1016/j.comptc.2015.10.034

Cited by 38 publications

(18 citation statements)

References 38 publications

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“…Both the aglycone and the glucosides are able to insert in the bilayer, although the aglycone has a deeper penetration. Such behavior has been observed in molecular dynamics simulations by Trouillas and coworkers for other polyphenol glycosides 86 . The sugar moiety forces the molecule to adopt a more superficial location in the membrane and establishes more hydrogen bonds with the hydration water and phospholipid headgroups.…”

Section: Resultssupporting

confidence: 52%

“…Moreover, we found that quercetin in POPC:cholesterol 1:1 bilayers, where it has superficial location, decreases the order parameters in POPC acyl chain carbons (C2–C9 in sn -1 and C2–C7 in sn -2) 64 . In addition, the polyphenol adopts a different orientation in the membrane when it is linked to a sugar 86 , 88 , which may also help to explain why 8-glucosylgenistein influences more membrane fluidity than its aglycone, genistein. On the other hand, the distinct location and orientation of the molecule may also explain the decreased ability of 8-glucosylgenistein to modify the membrane dipole potential.…”

Section: Resultsmentioning

confidence: 99%

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C-Glucosylation as a tool for the prevention of PAINS-induced membrane dipole potential alterations

Matos

Blázquez-Sánchez

Sousa

et al. 2021

Sci Rep

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The concept of Pan-Assay Interference Compounds (PAINS) is regarded as a threat to the recognition of the broad bioactivity of natural products. Based on the established relationship between altered membrane dipole potential and transmembrane protein conformation and function, we investigate here polyphenols' ability to induce changes in cell membrane dipole potential. Ultimately, we are interested in finding a tool to prevent polyphenol PAINS-type behavior and produce compounds less prone to untargeted and promiscuous interactions with the cell membrane. Di-8-ANEPPS fluorescence ratiometric measurements suggest that planar lipophilic polyphenols—phloretin, genistein and resveratrol—act by decreasing membrane dipole potential, especially in cholesterol-rich domains such as lipid rafts, which play a role in important cellular processes. These results provide a mechanism for their labelling as PAINS through their ability to disrupt cell membrane homeostasis. Aiming to explore the role of C-glucosylation in PAINS membrane-interfering behavior, we disclose herein the first synthesis of 4-glucosylresveratrol, starting from 5-hydroxymethylbenzene-1,3-diol, via C-glucosylation, oxidation and Horner-Wadsworth-Emmons olefination, and resynthesize phloretin and genistein C-glucosides. We show that C-glucosylation generates compounds which are no longer able to modify membrane dipole potential. Therefore, it can be devised as a strategy to generate bioactive natural product derivatives that no longer act as membrane dipole potential modifiers. Our results offer a new technology towards rescuing bioactive polyphenols from their PAINS danger label through C–C ligation of sugars.

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Section: Resultssupporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

C-Glucosylation as a tool for the prevention of PAINS-induced membrane dipole potential alterations

Matos

Blázquez-Sánchez

Sousa

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The overall binding free energies, which took all the interaction forces into account, was a more comprehensive measurement of binding affinity of ligands to receptors28. According to previous study, the higher negative of the binding free energies values, the stronger affinity of the ligand to the receptor29. To provide further insight into the interactions between dimers with lipid bilayer, the binding free energy for the dimer-bilayer complex was evaluated using MM/PBSA method.…”

Section: Resultsmentioning

confidence: 99%

Molecular Insight into Affinities of Gallated and Nongallated Proanthocyanidins Dimers to Lipid Bilayers

Zhu

Xiong

Peng

et al. 2016

Sci Rep

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Experimental studies have proved the beneficial effects of proanthocyanidins (Pas) relating to interaction with the cell membrane. But the detailed mechanisms and structure-function relationship was unclear. In present study, molecular dynamics (MD) simulations were used to study the interactions of four PA dimers with a lipid bilayer composed of 1:1 mixed 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE). The results showed that the gallated PA dimers had much higher affinities to the bilayer with lower binding free energies compared with nongallated PA dimers. The gallated PA dimers penetrated deeper into the bilayer and formed more hydrogen bonds (H-bonds) with bilayer oxygen atoms, especially the deeper oxygen atoms of the lipids simultaneously, thus inducing stronger lateral expansion of the membrane and lipid tails disorder. The present results provided molecular insights into the interactions between PA dimers and bio-membranes and agreed with our experimental results well. These molecular interactions helped to elucidate the structure-function relationship of the PA dimers and provided a foundation for a better understanding of the underlying mechanisms of the bioactivities of PA oligomers.

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“…For that purpose, the compounds should not only efficiently scavenge free radicals but also be inserted sufficiently deeply in the lipid bilayer. MD simulations can calculate the capacity of antioxidants to be inserted into lipid bilayers and, when available, to indicate their position and orientation in membranes with remarkable accuracy compared to experimental data [ 27 , 83 , 84 , 85 ]. Many antioxidants rapidly approach the lipid bilayers from the bulk water, and they partition in the membrane at different depths of insertion and orientation depending, to a major extent, on their lipophilic/hydrophilic/amphiphilic character.…”

Section: New Concepts In Oxidative Stressmentioning

confidence: 99%

Oxidative Stress Evaluation in Ischemia Reperfusion Models: Characteristics, Limits and Perspectives

Chazelas

Steichen

Favreau

et al. 2021

IJMS

Self Cite

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Ischemia reperfusion injury is a complex process consisting of a seemingly chaotic but actually organized and compartmentalized shutdown of cell function, of which oxidative stress is a key component. Studying oxidative stress, which results in an imbalance between reactive oxygen species (ROS) production and antioxidant defense activity, is a multi-faceted issue, particularly considering the double function of ROS, assuming roles as physiological intracellular signals and as mediators of cellular component damage. Herein, we propose a comprehensive overview of the tools available to explore oxidative stress, particularly in the study of ischemia reperfusion. Applying chemistry as well as biology, we present the different models currently developed to study oxidative stress, spanning the vitro and the silico, discussing the advantages and the drawbacks of each set-up, including the issues relating to the use of in vitro hypoxia as a surrogate for ischemia. Having identified the limitations of historical models, we shall study new paradigms, including the use of stem cell-derived organoids, as a bridge between the in vitro and the in vivo comprising 3D intercellular interactions in vivo and versatile pathway investigations in vitro. We shall conclude this review by distancing ourselves from “wet” biology and reviewing the in silico, computer-based, mathematical modeling, and numerical simulation options: (a) molecular modeling with quantum chemistry and molecular dynamic algorithms, which facilitates the study of molecule-to-molecule interactions, and the integration of a compound in a dynamic environment (the plasma membrane...); (b) integrative systemic models, which can include many facets of complex mechanisms such as oxidative stress or ischemia reperfusion and help to formulate integrated predictions and to enhance understanding of dynamic interaction between pathways.

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Interaction of wine anthocyanin derivatives with lipid bilayer membranes

Cited by 38 publications

References 38 publications

C-Glucosylation as a tool for the prevention of PAINS-induced membrane dipole potential alterations

C-Glucosylation as a tool for the prevention of PAINS-induced membrane dipole potential alterations

Molecular Insight into Affinities of Gallated and Nongallated Proanthocyanidins Dimers to Lipid Bilayers

Oxidative Stress Evaluation in Ischemia Reperfusion Models: Characteristics, Limits and Perspectives

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