Inhibition of Beta‐Amyloid Peptide Aggregation by Multifunctional Carbazole‐Based Fluorophores

Abstract

Aggregation ausgeschlossen: Carbazol‐basierte Cyaninfluorophore binden selektiv an das Aβ(1–40)‐Peptid und dessen Aggregate, die zur Entstehung der Alzheimer‐Krankheit führen. Ein solcher Fluorophor, SLOH, hemmt wirksam die Bildung von Aβ(1–40)‐Fibrillen (siehe Schema); da er die Blut‐Hirn‐Schranke passieren kann, ist er ein potenzielles Alzheimer‐Therapeutikum.

Multimodal Theranostic Cyanine-Conjugated Gadolinium(III) Complex for In Vivo Imaging of Amyloid-β in an Alzheimer’s Disease Mouse Model

“…24 To convert a clinically used MRI-active Gd(III) complex into a desirable and practically useful Aβ multimodal imaging probe, a multifunctional vehicle molecule that is biocompatible, NIR-emissive, two-photon absorption (TPA) active, BBB-permeable, and Aβ targetable could be integrated with it. In this work, we report the first BBB-permeable and Aβ-targeted Gd(III) complex-derived dyads synthesized by conjugation of Gd(DOTA) and carbazole-based cyanine 25 with different linkers, namely, Dyad-n, where n = 1−3 (Figure 1A), as multimodal contrast agents for imaging of Aβ species in vivo and ex vivo in the brains of mice in AD mouse models. Among the series, the facilely synthesized Dyad-3 was found to exhibit the most favorable functional properties, including good biocompatibility, low cytotoxicity, high Aβ selectivity, strong turn-on fluorescence upon interacting with Aβ species, large longitudinal relaxivity (r 1 ), high stability, good BBB penetrability, and fast elimination from the mouse, and was successfully applied for real-time multimodal imaging of Aβ species in a transgenic mouse model of AD.…”

Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism

“…Compound 11 (Figure 9) showed the most potent inhibitory activity against equine serum BChE ( eq BChE) with the SI of 52. N ‐benzylpyridinium combined with tetrahydro‐carbazole was disclosed by Ghobadian et al 167 Carbazole (Figure 9) contains a tricyclic structure that are common in selective BChE inhibitors, and the derivates were confirmed to show beneficial effects on treating AD through inhibiting self‐aggregation of Aβ 168 . Ghobadian et al 167 recently designed and synthesized a series of dual binding site BChE inhibitors based on the structure of N ‐benzylpyridinium combined with 2,3,4,9‐tetrahydro‐1 H ‐carbazole, which is a partial reduced form of carbazole.…”

A new fluorescent boronic acid sensor based on carbazole for glucose sensing via aggregation-induced emission

“…[13][14][15] Moreover, carbazole has been used widely as AIEgene. 16,17 However, its application is limited in biological systems due to poor water solubility and short excitation and emission wavelengths. 18 These disadvantages can be overcome by synthesizing water-soluble carbazole derivatives, which are capable exhibit an excimer emission wavelength in the visible region.…”