title: 2-Styrylindolium based fluorescent probes visualize neurofibrillary tangles in Alzheimer's disease.
abstract: We evaluated 2-styrylindolium derivatives (6-11) as novel and selective probes for neurofibrillary tangles (NFTs) on brain sections of AD patients. The staining experiments indicated that these compounds may bind selectively to NFTs in the presence of ß-amyloid (Aß) plaques. Cell free binding assays confirmed that 2-[2-[4-(1-pyrrolidinyl)phenyl]ethenyl]-1,3,3-trimethyl-3H-indolium iodide (9) and 2-[2-[4-(diethylamino)phenyl]ethenyl]-1-butyl-3,3-dimethyl-3H-indolium iodide (11) display excellent affinities to Tau-aggregates (IC(50) values of 5.1 and 1.4 nM, respectively) in the displacement of Thiazin Red R. These probes have good solubility in distilled water and low or no cytotoxicity in zebrafish embryo and liver hepatocellular carcinoma cell assays.
authors.affiliation: Clemens Schöpf Institute of Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstrasse 22, Darmstadt 64287, Germany.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Gu
authors.forename: Upendra Rao
authors.initials: UR
authors.lastname: Anumala
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: Valérie
authors.initials: V
authors.lastname: Goetschy-Meyer
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: Boris
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D016874:Neurofibrillary Tangles / Q000473:pathology*; D013329:Structure-Activity Relationship; D015027:Zebrafish
chemical_list: C581119:2-styrylindolium; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D007211:Indoles