Unfolding the Role of a Flavone-Based Fluorescent Antioxidant towards the Misfolding of Amyloid Proteins: An Endeavour to Probe Amyloid Aggregation

Abstract

4′-N,N-Dimethylamino-3-hydroxyflavone (DMAHF), a synthetic fluorescent flavone analogue with potent antioxidant activity, was explored as a molecular rotor-like fluoroprobe for amyloid aggregations, a causative factor in Alzheimer's disease, Parkinson's disease, type-2 diabetes, etc. During its interactions with (human) insulin amyloid aggregation (IAA), its microenvironment was changed. This instigated a drastic change in its excited-state intramolecular proton transfer-based dual emission behavior, which was tracked to monitor its amyloid probing activity. Thus, the amyloid probing potential of DMAHF was originated from its interactions with IAA, which were studied by various spectroscopic techniques and molecular docking and quantum-mechanical calculations. Morphological changes of the IAA in the presence of DMAHF were studied by scanning electron microscopy. DMAHF also probed efficiently the islet amyloid polypeptide deposition in the pancreatic β-cells of diabetic mice. DMAHF showed significant sensitivity and specificity towards amyloid aggregation without having any complexity in its photophysical behavior. This indicates its potential as an ideal bio-friendly and cost-effective fluoroprobe for amyloid proteins.

Insights into interactions between food polyphenols and proteins: An updated overview

“…Whereas the polyphenol-protein complexes can effectively prevent fibrillation and form altered aggregation, which is non-toxic to human health. Therefore, polyphenols can be used as inhibitors of protein pathological aggregation through the protein-binding pathway (Karmakar et al, 2020;Matos et al, 2019;Thapa et al, 2016).…”

“…Whereas the polyphenol–protein complexes can effectively prevent fibrillation and form altered aggregation, which is non‐toxic to human health. Therefore, polyphenols can be used as inhibitors of protein pathological aggregation through the protein‐binding pathway (Karmakar et al, 2020; Matos et al, 2019; Thapa et al, 2016). Figure 3 shows the anti‐aggregation and fibril remodeling of polyphenol on amyloid beta (Aβ) amyloid formation and interaction mechanism at the molecular level.…”

“…Figure 3 shows the anti‐aggregation and fibril remodeling of polyphenol on amyloid beta (Aβ) amyloid formation and interaction mechanism at the molecular level. Scientifically, Figure 3a illustrates remodeled Aβ amyloid fibrils markedly differed from the self‐aggregated fibrils, which had highly physiological toxicity due to the combination with polyphenols (Kai et al, 2015; Karmakar et al, 2020; Matos et al, 2019; Thapa et al, 2016). The detailed explanation is presented in Figure 3b,c.…”

“…On the one hand, the microenvironment of polyphenols will change after polyphenol–protein complexes are formed, which can be measured as the characterization of interactions. Corresponding to the protocol, Karmakar et al studied the probing role of 4′‐N,N‐dimethylamino‐3‐hydroxyflavone (DMAHF) toward the amyloid aggregation based on their non‐covalent interaction (Karmakar et al, 2020). It was characterized by fluorescence spectrum of DMAHF with quantum‐chemically calculation during the interaction process, so as to explain the interaction mechanism and evaluate insulin amyloid aggregation.…”

Structural Features of a Family of Coumarin–Enamine Fluorescent Chemodosimeters for Ion Pairs

“…This often leads to large changes in the optical response of these molecules, such as large Stokes shifts in luminescence emission (>200 nm), as well as new absorbance and emission signals. Several fluorophores incorporate the cyclic RAHB motif, including hydroxy- and amino-substituted 2-arylbenzoxazole (HBO), , 2-arylbenzothiazole (HBT), and anthraquinone (AQ) − as well as 3-hydroxyflavone (3HF) derivatives − (Figure ). In these compounds, the enol tautomer ( E ) has a distinct UV–vis absorption from the keto tautomer ( K ).…”