Vanillin Benzothiazole Derivative Reduces Cellular Reactive Oxygen Species and Detects Amyloid Fibrillar Aggregates in Alzheimer’s Disease Brain

Abstract

The misfolding of amyloid beta (Aβ) peptides into Aβ fibrillary aggregates is a major hallmark of Alzheimer's disease (AD), which responsible for the excess production of hydrogen peroxide (H 2 O 2 ), a prominent reactive oxygen species (ROS) from the molecular oxygen (O 2 ) by the reduction of the Aβ-Cu(I) complex. The excessive production of H 2 O 2 causes oxidative stress and inflammation in the AD brain. Here, we have designed and developed a dual functionalized molecule VBD by using π-conjugation (C�C) in the backbone structure. In the presence of H 2 O 2 , the VBD can turn into fluorescent probe VBD-1 by cleaving of the selective boronate ester group. The fluorescent probe VBD-1 can undergo intramolecular charge transfer transition (ICT) by a πconjugative system, and as a result, its emission increases from the yellow (532 nm) to red (590 nm) region. The fluorescence intensity of VBD-1 increases by 3.5-fold upon binding with Aβ fibrillary aggregates with a high affinity (K d = 143 ± 12 nM). Finally, the VBD reduces the cellular toxic H 2 O 2 as proven by the CCA assay and DCFDA assay and the binding affinity of VBD-1 was confirmed by using in vitro histological staining in 8-and 18-month-old triple transgenic AD (3xTg-AD) mice brain slices.

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…Copper( ii ) with and without Aβ may both be reduced to copper( i ) in the cellular environment that contains reducing agents (such as ascorbate and glutathione), as illustrated in copper( i )-Aβ may interact with O 2 to create ROS, such as O 2− , H 2 O 2 , and OH, which can oxidatively modify Aβ and alter its aggregation. 141–143 The copper binding sites and binding modes of monomeric Aβ peptides are flexible, and they alter dynamically with pH (Fig. 6 top (a) and (b)) and oxidation state as well as the metal centres’ responsiveness to ligand replacement and redox catalysis 136 (fig below).…”

Logic “AND Gate Circuit” Based Mussel Inspired Polydopamine Nanocomposite as Bioactive Antioxidant for Management of Oxidative Stress and Neurogenesis in Traumatic Brain Injury

“…The potential of PDA-AMSNs to mitigate the effects of ROS was also assessed through a coumarin-3-carboxylic acid (CCA) assay. 37 CCA assay is a fluorescent detection method to detect • OH (hydroxyl radical) in aqueous solution. In the present analysis, the reducing agent ascorbate facilitates the conversion of Cu 2+ to Cu + .…”

“…To evaluate the redox silencing activity of our nanoparticles, a CCA assay was performed according to our previously reported protocol. 37 Briefly, it includes incubation of nonfluorescent compound coumarin-3-carboxylic acid (CCA, 150 μM), Cu 2+ (10 μM), and PDA-AMSN or ascorbic acid (10 μM) separately in PBS (0.1 mM, pH = 7.4) at 37 °C. Further, the fluorescent excitation and emission intensity were measured (λ ex = 385 nm, λ em = 452 nm) in the thermo VarioLux scan microplate reader.…”

Power of Dopamine: Multifunctional Compound Assisted Conversion of the Most Risk Factor into Therapeutics of Alzheimer’s Disease

“…If any molecule is capable of capturing copper from the Aβ-Cu 2+ complex, it will also prevent ROS production. Therefore, to check the effect of SB on ROS generation, we have performed a DCFDA assay. ,, DCFDA measures the different ROS such as hydroxyl and peroxyl groups within the cell. The cellular esterase deacetylated the nonfluorescent DCFDA into a nonfluorescent compound, which was further oxidized by the ROS to the highly fluorescent DCF in the cell.…”