Thiophene‐π‐Cyanoacetamides Show Intense and Tau‐selective Turn‐on Fluorescence in the Near‐Infrared Region

Abstract

Investigations into tau-targeting diagnosis of Alzheimer's disease are currently underway, and the development of tau-selective molecular probes is urgently required. In this study, the donor-π-acceptor architecture of the previously reported tau-selective fluorescence probe was modified into thiophene-π-cyanoacetamides. While the fluorescence properties of the prepared probes were not influenced by the thiophene substituents, intense and tau-selective turn-on fluorescence in the near infrared region was observed only in the probes with unsubstituted phenyl or p-methylphenyl cyanoacetamides in the acceptor functionality. Compared with the parent compound, the newly identified probes showed 1.5 $ 4.1 times increase in tau-selectivity over Aβ fibrils and 3.5 $ 4.7 times increase in fluorescence intensity. The tau-selective fluorescence properties of the title probes were further demonstrated in the cellular milieu, and the green and red fluorescence emitted by GFP and tau-bound probes, respectively, were shown to be nicely colocalized in the SH-SY5Y cells stably expressing GFP-tagged tau.

Recent advances in small molecular near-infrared fluorescence probes for a targeted diagnosis of the Alzheimer disease

“…Furthermore, a series of probes including 2-dimethylamino ( 2a–2g ) and 2-morpholino ( 3a–3g ) thiophene derivatives were synthesized, and the probes have different substituted α-cyanoacetamide functions at the end of the conjugate linker (thiophene-π-cyanoacetamide). 121 Among all the probes, it was found that only phenyl or p -methyl-substituted phenyl cyanoacetamides ( 2a , 2b , 3a , and 3b ), which were not substituted, could selectively recognize Tau fibrils and offer the turn-on fluorescence emission in the NIR range ( λ em = 705 to 710 nm) (Fig. 8e–h).…”

“…Both monomeric and fibrillar forms of tau were evaluated for fluorescence staining by the probe molecules. 121 Copyright 2021, Wiley Online Library. strong hydrogen bonds, in which the probe has both the N atom in the pyrimidine ring and the O atom of the amide bond (Fig.…”

“…Fluorescence spectra of 50 μM of (e) 2a, (f) 2b, (g) 3a, and (h) 3b in the absence or presence of tau, Aβ and BSA. Both monomeric and fibrillar forms of tau were evaluated for fluorescence staining by the probe molecules 121. Copyright 2021, Wiley Online Library.…”

Small Molecular Fluorescent Probes for Alzheimer's Disease Associated Active Species

“…Chong and colleagues synthesized two series of Tauselective thiophene derivatives by combining a dimethylamino or a morpholine modified thiophene ring with different amide units through conjugated skeleton. [78] The authors comprehensively explored the characters of theses probes, including spectra response to Tau and other analogues, fluorescence properties, selectivity due to the structural differences. All the data demonstrated that four probes 36 a-36 d (Figure 6) possessed superior properties.…”

Recent Developments in PET and SPECT Radiotracers as Radiopharmaceuticals for Hypoxia Tumors

“…Molecular imaging is defined as the visualization, characterization, and quantification of biological processes in intact living subjects using specific imaging probes [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Nowadays, molecular imaging technologies provide insights into biological events, pathology, and the mechanisms of diseases; thus, they play an important role in various fields of neuroscience, cardiology, gene therapy, oncology, and so on [ 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ].…”