2-Styrylindolium based fluorescent probes visualize neurofibrillary tangles in Alzheimer’s disease

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 24; pp. 7667 - 7671
• Main Authors: Gu, Jiamin, Anumala, Upendra Rao, Lo Monte, Fabio, Kramer, Thomas, Heyny von Haußen, Roland, Hölzer, Jana, Goetschy-Meyer, Valérie, Mall, Gerhard, Hilger, Ingrid, Czech, Christian, Schmidt, Boris
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 15.12.2012; Elsevier
• Subjects: Alzheimer disease; Alzheimer Disease - diagnosis; Alzheimer’s disease; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; brain; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Cytotoxicity; Danio rerio; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Embryo, Nonmammalian - drug effects; fluorescence; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacology; Hep G2 Cells; hepatoma; Humans; Imaging; Indoles - chemistry; Indoles - pharmacology; inhibitory concentration 50; iodides; Life Sciences & Biomedicine; liver; Medical sciences; Molecular Structure; Neurofibrillary tangles; Neurofibrillary Tangles - pathology; patients; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Science & Technology; solubility; Structure-Activity Relationship; Zebrafish; YNVCGZRAQOHCEC-UHFFFAOYSA-M; Neurofibrillary tangles; BYUCENOZTGVBAU-UHFFFAOYSA-M; Alzheimer’s disease; DFMPGFLPNGLYSZ-UHFFFAOYSA-M; Imaging; IPOZUTQBTFRBLZ-UHFFFAOYSA-N; Zebrafish; Cytotoxicity; GUNZDBGLCFMCGT-UHFFFAOYSA-M; IRPSTTBCEOBEMW-JHGYPSGKSA-M; RED; A-BETA PLAQUES; AMYLOID PLAQUES; TAU; PATHOLOGY; IMAGING AGENTS; Alzheimer's disease; DERIVATIVES; Nervous system diseases; Alzheimer disease; Neurofibrillary tangle; Cerebral disorder; Vertebrata; Brachydanio rerio; Pisces; Central nervous system disease; Medical imagery; Degenerative disease; Fluorescent compound
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.09.109

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 (IC50 values of 5.1 and 1.4nM, 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.