Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer’s Disease Agents

Poliseno, Viviana; Chaves, Sı́lvia; Brunetti, Leonardo; Loiodice, Fulvio; Carrieri, Antonio; Laghezza, Antonio; Tortorella, Paolo; Magalhães, João Duarte; Cardoso, Sandra M.; Santos, M. Amélia; Piemontese, Luca

doi:10.3390/biom11010111

Cited by 23 publications

(11 citation statements)

References 53 publications

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“…In plant cells, it inhibits the proton pump of the plasma membrane and photosynthesis [ 80 , 81 ], being one of the pathogenicity factors of phytopathogenic fungi that produce it [ 82 ]. Cell-free assays demonstrated TeA to be an antioxidant and a promising inhibitor of acetylcholinesterase and β-amyloid aggregation [ 83 , 84 ]. TeA is toxic to rodents and chickens, causing diarrhea, bleeding, and precancerous conditions.…”

Section: Discussionmentioning

confidence: 99%

Entomotoxic Activity of the Extracts from the Fungus, Alternaria tenuissima and Its Major Metabolite, Tenuazonic Acid

Salimova

Dalinova

Dubovik

et al. 2021

JoF

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The study of fungal antibiotics in their competitive interactions with arthropods may lead to the development of novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained using various methods showed a wide range of biological activities, including entomotoxic properties. Analysis of their composition and bioactivity allowed us to reveal several known mycotoxins and unidentified compounds that may be involved in the entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with an LT50 of 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited the growth of G. mellonella larvae and caused mortality of Acheta domesticus adults (LT50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing 15% and 27% mortality at a concentration of 1 mg/mL, respectively. TeA was cytotoxic to the Sf9 cell line (IC50 25 µg/mL). Thus, model insects such as G. mellonella could be used for further toxicological characterization of TeA.

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Section: Discussionmentioning

confidence: 99%

Entomotoxic Activity of the Extracts from the Fungus, Alternaria tenuissima and Its Major Metabolite, Tenuazonic Acid

Salimova

Dalinova

Dubovik

et al. 2021

JoF

View full text Add to dashboard Cite

show abstract

“…In plant cells, it inhibits the proton pump of the plasma membrane and photosynthesis [80,81], being one of the pathogenicity factors of phytopathogenic fungi producing it [82]. Cell-free assays demonstrated TeA to be an antioxidant and a promising inhibitor of acetylcholinesterase and β-amyloid aggregation [83,84]. TeA is toxic to rodents and chickens, causing diarrhea, bleeding and precancerous conditions.…”

Section: Tenuazonic Acid As a Model Moleculementioning

confidence: 99%

Entomotoxic Activity of the Extracts from the Fungus, <em>Alternaria tenuissima</em> and Its Major Metabolite, Tenuazonic Acid

Salimova¹,

Dalinova²,

Dubovik³

et al. 2021

Preprint

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Study of fungal antibiotics in their competitive interactions with arthropods may lead to development novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained by various methods showed a wide range of biological activity, including entomotoxic properties. Analysis of their composition and bioactivity allowed to reveal several known mycotoxins and unidentified compounds that may be involved in entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with LT50 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited growth of G. mellonella larvae and caused mortality of Acheta domesticus imagines (LT50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact-intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing the 12 and 40% of mortality at a concentration of 1 mg/mL. TeA was cytotoxic to Sf9 cell line (IC50 25 µg/mL). Thus, model insect G. mellonella and cell line Sf9 could be used for a further toxicological characterization of TeA.

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“…For example, Resveratrol, a polyphenolic phytoalexin from medicinal plants, grapes, peanuts, and red wines, decreases reactive oxygen species (3), inhibits Aβ 1-42 aggregation and exerts neuroprotective effects ( Li et al, 2014 ). A series of natural products like hesperidin ( Chakraborty et al, 2016 ), matrine ( Cui et al, 2017 ), tenuazonic acid ( Poliseno et al, 2021 ) and licochalcone ( Liu et al, 2021 ) display therapeutic potentials of AD by participating in two or more regulative means, including acetylcholinesterase (AChE) inhibition, metal chelation and anti-neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

Multifunctional Anti-Alzheimer’s Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation

Lee

Wang

et al. 2022

Front. Chem.

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Background: A series of α-Mangostin (α-M) derivatives were designed and synthesized. α-M and four analogues were evaluated for their multifunctional anti-Alzheimer’s disease (anti-AD) effects on fibrillogenesis, microglial uptake, microglial degradation, and anti-neurotoxicity of Aβ, as well as LPS-induced neuroinflammation. The differences in bioactivities were analyzed to understand the structure-activity relationship for further modifications.Purpose: This study aims to investigate the anti-AD effects of α-M and elucidate its structure-activity relationship by comparing difference between α-M and several analogues.Methods: Aβ fibrillogenesis was detected by Thioflavin T fluorometric assay. The levels of Aβ1-42 and inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Neuron viability was examined by the CCK-8 assay. The morphology of ZO-1 of bEnd.3 cultured in BV-2-conditioned medium was evaluated by immunofluorescence staining.Results: Aβ fibrillogenesis was significantly inhibited by co-incubation with α-M, Zcbd-2 or Zcbd-3. α-M, Zcbd-2, Zcbd-3, and Zcbd-4 decreased the levels of Aβ1-42 and inflammatory cytokines, and promoted Aβ uptake, degradation and anti-inflammation effects inflammation in microglia. α-M and Zcbd-3 protected neuron viability from Aβ-induced neurotoxicity, and preserved tight junction integrity of bEnd.3 against LPS-induced neuroinflammation.Conclusion: Zcbd-3 acted as α-M almost in all effects. The structure-activity analysis indicated that the 3-methyl-2-butenyl group at C-8 is essential for the bioactivity of α-M, while modifying the double hydroxylation at the C-2 position may improve the multifunctional anti-AD effects.

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Derivatives of Tenuazonic Acid as Potential New Multi-Target Anti-Alzheimer’s Disease Agents

Cited by 23 publications

References 53 publications

Entomotoxic Activity of the Extracts from the Fungus, Alternaria tenuissima and Its Major Metabolite, Tenuazonic Acid

Entomotoxic Activity of the Extracts from the Fungus, Alternaria tenuissima and Its Major Metabolite, Tenuazonic Acid

Entomotoxic Activity of the Extracts from the Fungus, <em>Alternaria tenuissima</em> and Its Major Metabolite, Tenuazonic Acid

Multifunctional Anti-Alzheimer’s Disease Effects of Natural Xanthone Derivatives: A Primary Structure-Activity Evaluation

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