Title Autoxidation enhances anti-amyloid potential of flavone derivatives /
Authors Sakalauskas, Andrius ; Žiaunys, Mantas ; Sniečkutė, Rūta ; Smirnovas, Vytautas
DOI 10.3390/antiox10091428
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Is Part of Antioxidants.. Basel : MDPI. 2021, vol. 10, iss. 9, art. no. 1428, p. [1-13].. eISSN 2076-3921
Keywords [eng] aggregation ; amyloid-beta ; autoxidation ; flavones ; inhibition ; insulin
Abstract [eng] 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.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2021
CC license CC license description