title: 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 (Kd= 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.
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.
authors.forename: Pascal
authors.identifier: 0000-0002-4442-1734
authors.initials: P
authors.lastname: Dao
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.
authors.forename: Zhi Yun
authors.initials: ZY
authors.lastname: Du
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.|Université Paris Diderot, Sorbonne Paris Cité , ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Cedex 13 Paris, France.
authors.forename: Chang Zhi
authors.initials: CZ
authors.lastname: Dong
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.|Laboratoire, de Chimie de Coordination du CNRS , 205 Route de Narbonne, 31077 Cedex Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
authors.affiliation: Faculty of Light Industry and Chemical Engineering, Guang Dong University of Technology , Guangzhou, Guang Dong 510006, China.|CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes PRES Sorbonne Paris Cité, UFR Biomédicale , 45 rue des Saints-Pères, 75270 Cedex 06 Paris, France.
authors.forename: Huixiong
authors.identifier: 0000-0001-7676-1584
authors.initials: H
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D000818:Animals; D004195:Disease Models, Animal; D042241:Early Diagnosis; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D059906:Neuroimaging / Q000379:methods*; D061848:Optical Imaging / Q000379:methods*; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000175:diagnosis; D019265:Spectroscopy, Near-Infrared; D000068936:Theranostic Nanomedicine / Q000379:methods
chemical_list: D005456:Fluorescent Dyes; D010640:Phenothiazines
keywords: Alzheimer’s disease; NIRF imging; cytotoxicity; inhibitors; theranostic agents; β-amyloid