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

Bioorg Med Chem Lett. 2012 Dec 15;22(24):7667-71. doi: 10.1016/j.bmcl.2012.09.109. Epub 2012 Oct 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Embryo, Nonmammalian / drug effects
  • Fluorescent Dyes* / chemistry
  • Fluorescent Dyes* / pharmacology
  • Hep G2 Cells
  • Humans
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Molecular Structure
  • Neurofibrillary Tangles / pathology*
  • Structure-Activity Relationship
  • Zebrafish

Substances

  • 2-styrylindolium
  • Antineoplastic Agents
  • Fluorescent Dyes
  • Indoles