title: Fluorescent rhodanine-3-acetic acids visualize neurofibrillary tangles in Alzheimer's disease brains.
abstract: There is a high demand for the development of an imaging agent for neurofibrillary tangles (NFTs) detection in Alzheimer's diagnosis. In the present study, a series of rhodanine-3-acetic acids was synthesized and evaluated for fluorescence imaging of NFTs in brain tissues of AD patients. Five out of seven probes have shown excellent binding affinity to NFTs over amyloid plaques in the Thiazine red R displacement assay. However, the selectivity in this in vitro assay is not confirmed by the histopathological evaluation, which indicates significant differences in the binding sites in the assays. Probe 6 showed binding affinity (IC50=19nM) to tau aggregates which is the highest among this series. Probes 2, 3, 4 and 5 display IC50 values of lower than 100nM to tau aggregates to displace Thiazine red R. Evaluation of the cytotoxicity of these five probes with human liver carcinoma cells revealed that these compounds excert negligible cytotoxicity. The in vivo studies with zebrafish embryos confirmed negligible cytotoxicity at 24 and 72h post fertilization.
authors.affiliation: Clemens Schöpf-Institute of Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstrasse 22, Darmstadt 64287, Germany.
authors.forename: Upendra Rao
authors.initials: UR
authors.lastname: Anumala
authors.forename: Jiamin
authors.initials: J
authors.lastname: Gu
authors.forename: Fabio
authors.initials: F
authors.lastname: Lo Monte
authors.forename: Thomas
authors.initials: T
authors.lastname: Kramer
authors.forename: Roland
authors.initials: R
authors.lastname: Heyny-von Haußen
authors.forename: Jana
authors.initials: J
authors.lastname: Hölzer
authors.forename: Valerie
authors.initials: V
authors.lastname: Goetschy-Meyer
authors.forename: Christian
authors.initials: C
authors.lastname: Schön
authors.forename: Gerhard
authors.initials: G
authors.lastname: Mall
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
authors.forename: Christian
authors.initials: C
authors.lastname: Czech
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012236:Rhodanine / Q000737:chemistry*; D015027:Zebrafish / Q000254:growth & development; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000085:Acetates; D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; C054369:MAPT protein, human; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D012236:Rhodanine
keywords: Alzheimer’s disease; Cytotoxicity; Fluorescence imaging; Neurofibrillary tangles; Zebrafish