Development of Phenothiazine-Based Theranostic Compounds That Act Both as Inhibitors of β-Amyloid Aggregation and as Imaging Probes for Amyloid Plaques in Alzheimer’s Disease
Abstract
Early detection of Alzheimer’s disease (AD) is imperative in enabling the understanding and clinical treatment of this disorder, as well as in preventing its progression. Imaging agents specifically targeting Aβ plaques in the brain and the retina may lead to the early diagnosis of AD. Among them, near-infrared fluorescent (NIRF) imaging has emerged as an attractive tool to noninvasively identify and monitor diseases during the preclinical and early stages. In the present study, we report the design, synthesis, and evaluation of a series of new near-infrared fluorescent probes. Most of these probes displayed maximum emission in PBS (>650 nm), which falls in the good range for NIRF probes. Among them, 4a1 showed the highest affinity toward Aβ aggregates ( K d = 7.5 nM) and an excellent targeting ability for Aβ plaques in slices of brain and retina tissue from double transgenic mice. These compounds are also found to effectively prevent Aβ fibril formation and disaggregate preformed Aβ fibrils, showing a promising potential as theranostic agents for the diagnosis and therapy of AD.
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These derivatives can prevent aggregation of Aβ plaque and break already formed Aβ fibrils.
“These derivatives also have the ability to prevent the aggregation of Aβ plaque and break already formed Aβ fibrils.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [106]
Dao et al. (2017) synthesized phenothiazine derivatives that work as near infra-red fluorescent probes, have high affinity for amyloid plaque and can detect it in brain and retinal tissue of transgenic mice.
“Dao et al. (2017) have synthesized phenothiazine derivatives which work as near infra-red fluorescent probes, having a high affinity for the amyloid plaque and can detect it in the brain and retinal tissue of transgenic mice [106].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [106]
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Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease
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“(2017) have synthesized phenothiazine derivatives which work as near infra-red fluorescent probes, having a high affinity for the amyloid plaque and can detect it in the brain and retinal tissue of transgenic mice [106].”
BackgroundFrancisco, T. N., Malafaia, D., Melo, L., Silva, A. M. S., & Albuquerque, H. M. T. (2024) · ACS Omega · doi:10.1021/acsomega.3c10417 · Cited by 18 · see citing works
- Authors
- Dao, P., Ye, F., Liu, Y., Du, Z. Y., Zhang, K., Dong, C. Z., Meunier, B., & Chen, H.
- Affiliations
- Guangdong University of Technology (CN)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Chen, Huixiong
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-02-02
- Volume
- 8
- Issue
- 4
- Pages
- 798-806
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W2571955885
- Cited by
- 80
- References
- 26
- Citations by year
- 2025: 11 · 2024: 14 · 2023: 19 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 3
- FWCI
- 4.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China Postdoctoral Science Foundation (2015M572280)
- China Science Foundation (21672043)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence and Fluorescent Materials
- Keywords
- phenothiazines, theranostic agents, Alzheimer's disease, amyloid-beta aggregation, amyloid plaques, near-infrared fluorescent probe, amyloid imaging, fibril disaggregation, double transgenic mice, retina, brain slices, early diagnosis
- MeSH terms
- Theranostic Nanomedicine, Alzheimer Disease, Animals, Disease Models, Animal, Fluorescent Dyes, Mice, Transgenic, Phenothiazines, Spectroscopy, Near-Infrared, Early Diagnosis, Mice, Plaque, Amyloid, Neuroimaging, Optical Imaging
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