Autoxidation Enhances Anti-Amyloid Potential of Flavone Derivatives
| Autor: | Vytautas Smirnovas, Andrius Sakalauskas, Mantas Ziaunys, Ruta Snieckute |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
insulin
Amyloid Physiology Amyloid beta Clinical Biochemistry Kinetics RM1-950 Protein aggregation Biochemistry Flavones Article aggregation amyloid-beta autoxidation flavones inhibition Absorbance Molecule Molecular Biology chemistry.chemical_classification biology Autoxidation Chemistry Cell Biology biology.protein Biophysics Therapeutics. Pharmacology |
| Zdroj: | Antioxidants, Basel : MDPI, 2021, vol. 10, iss. 9, art. no. 1428, p. [1-13] Antioxidants Volume 10 Issue 9 Antioxidants, Vol 10, Iss 1428, p 1428 (2021) |
| ISSN: | 2076-3921 |
| DOI: | 10.3390/antiox10091428 |
| Popis: | The increasing prevalence of amyloid-related disorders, such as Alzheimer’s or Parkinson’s disease, raises the need for effective anti-amyloid drugs. It has been shown on numerous occasions that flavones, a group of naturally occurring anti-oxidants, can impact the aggregation process of several amyloidogenic proteins and peptides, including amyloid-beta. Due to flavone autoxidation at neutral pH, it is uncertain if the effective inhibitor is the initial molecule or a product of this reaction, as many anti-amyloid assays attempt to mimic physiological conditions. In this work, we examine the aggregation-inhibiting properties of flavones before and after they are oxidized. The oxidation of flavones was monitored by measuring the UV-vis absorbance spectrum change over time. The protein aggregation kinetics were followed by measuring the amyloidophilic dye thioflavin-T (ThT) fluorescence intensity change. Atomic force microscopy was employed to image the aggregates formed with the most prominent inhibitors. We demonstrate that flavones, which undergo autoxidation, have a far greater potency at inhibiting the aggregation of both the disease-related amyloid-beta, as well as a model amyloidogenic protein—insulin. Oxidized 6,2′,3′-trihydroxyflavone was the most potent inhibitor affecting both insulin (7-fold inhibition) and amyloid-beta (2-fold inhibition). We also show that this tendency to autoxidize is related to the positions of the flavone hydroxyl groups. |
| Databáze: | OpenAIRE |
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