Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors

González‐Cofrade, Laura; Green, Jack; Cuadrado, Irene; Amesty, Ángel; Oramas‐Royo, Sandra; Brough, David; Estévez‐Braun, Ana; Hortelano, Sonsoles; Herrero, Beatriz de las Heras

doi:10.1016/j.bioorg.2023.106362

Cited by 8 publications

(3 citation statements)

References 80 publications

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“…Recently, a study on the potential anti-inflammatory activity of some phenolic and methide-quinone nor -triterpenes isolated from Maytenus retusa that were evaluated for the inhibition of the NLRP3 inflammasome in macrophages appeared [ 35 ]. One of the most potent compounds evaluated was a semisynthetic methide-quinone Br derivative related to the three methide-quinones described in this work.…”

Section: Discussionmentioning

confidence: 99%

“…The calculated binding energies of these three compounds are −13.7 kcal/mol for hydroxytingenone, −11.8 and 13.0 kcal/mol for tingenone, and −9.3 and −9.4 kcal/mol for pristimerin, which indicate that all three natural products are good inhibitors. Each of these methide-quinones is closely related to the methide-quinone Br derivative mentioned above [ 35 ]. That these interactions remain after the more rigorous molecular dynamics calculations underscores their significance.…”

Section: Discussionmentioning

confidence: 99%

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Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques

Caruso

Rossi

Eberhardt

et al. 2023

IJMS

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The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body’s endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone’s other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L’Héritier) DC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques

Caruso

Rossi

Eberhardt

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…The prospect of clinical intervention of regulated necrosis pathways, such as disulfiram to inhibit GSDM pore formation (63), NLRP3 inflammasome inhibitors (55), and RIPK1 inhibitors (103), has also been investigated for the therapeutic treatment of inflammatory and degenerative diseases by intervening in necroptotic signaling, for use against inflammatory bowel disease, amyotrophic lateral sclerosis, and Alzheimer's disease (35,103,122).…”

Section: Exploiting Cell Death Therapeuticallymentioning

confidence: 99%

Programmed Cell Death in Unicellular Versus Multicellular Organisms

Kulkarni,

Hardwick

2023

Annu. Rev. Genet.

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Programmed cell death (self-induced) is intrinsic to all cellular life forms, including unicellular organisms. However, cell death research has focused on animal models to understand cancer, degenerative disorders, and developmental processes. Recently delineated suicidal death mechanisms in bacteria and fungi have revealed ancient origins of animal cell death that are intertwined with immune mechanisms, allaying earlier doubts that self-inflicted cell death pathways exist in microorganisms. Approximately 20 mammalian death pathways have been partially characterized over the last 35 years. By contrast, more than 100 death mechanisms have been identified in bacteria and a few fungi in recent years. However, cell death is nearly unstudied in most human pathogenic microbes that cause major public health burdens. Here, we consider how the current understanding of programmed cell death arose through animal studies and how recently uncovered microbial cell death mechanisms in fungi and bacteria resemble and differ from mechanisms of mammalian cell death. Expected final online publication date for the Annual Review of Genetics, Volume 57 is November 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Neuroinflammation Targeting Pyroptosis: Molecular Mechanisms and Therapeutic Perspectives in Stroke

Yuan,

Xia,

Jiang

et al. 2024

Mol Neurobiol

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Phenolic and quinone methide nor-triterpenes as selective NLRP3 inflammasome inhibitors

Cited by 8 publications

References 80 publications

Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques

Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques

Programmed Cell Death in Unicellular Versus Multicellular Organisms

Neuroinflammation Targeting Pyroptosis: Molecular Mechanisms and Therapeutic Perspectives in Stroke

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