Novel (E)-5-styryl-2,2'-bithiophene derivatives as ligands for β-amyloid plaques

Mengchao Cui; Zijing Li; Ruikun Tang; Hongmei Jia; Boli Liu

doi:10.1016/j.ejmech.2011.04.015

Novel (E)-5-styryl-2,2'-bithiophene derivatives as ligands for β-amyloid plaques

Eur J Med Chem. 2011 Jul;46(7):2908-16. doi: 10.1016/j.ejmech.2011.04.015. Epub 2011 Apr 12.

Authors

Mengchao Cui¹, Zijing Li, Ruikun Tang, Hongmei Jia, Boli Liu

Affiliation

¹ Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Xinjiekouwai Street 19#, Beijing 100875, PR China.

PMID: 21531050
DOI: 10.1016/j.ejmech.2011.04.015

Abstract

In continuation of our investigation on the bithiophene structure as potential β-amyloid probes, a series of (E)-5-styryl-2,2'-bithiophene (SBTP) derivatives was designed and synthesized. In vitro binding showed that all of them displayed high binding affinities to Aβ(1-42) aggregates (K(i)=0.10-41.05nM). Moreover, two radio-iodinated probes, [(125)I]-(E)-5-(4-iodostyryl)-2,2'-bithiophene ([(125)I]8) and [(125)I]-(E)-5-iodo-5'-(4-methoxystyryl)-2,2'-bithiophene ([(125)I]31) were prepared. Both of them displayed specific labeling of Aβ plaques in the brain sections of AD model mice with low background. In vivo biodistribution in normal mice indicated that [(125)I]8 exhibited high initial brain uptake (2.11% ID/g at 2 min) and rapid clearance (0.41% ID/g at 30 min). These preliminary results suggest that SBTP derivatives may be served as novel β-amyloid imaging probes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / diagnosis*
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid beta-Peptides / chemistry*
Animals
Biological Transport
Brain / diagnostic imaging
Brain / metabolism
Brain / pathology
Contrast Media / chemical synthesis*
Contrast Media / pharmacokinetics
Disease Models, Animal
Female
Humans
Iodine Radioisotopes
Ligands
Mice
Mice, Transgenic
Peptide Fragments / chemistry*
Plaque, Amyloid / diagnosis*
Plaque, Amyloid / diagnostic imaging
Plaque, Amyloid / metabolism
Plaque, Amyloid / pathology
Positron-Emission Tomography
Protein Binding
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / pharmacokinetics
Thiophenes / chemical synthesis*
Thiophenes / pharmacokinetics
Tomography, Emission-Computed, Single-Photon

Substances

Amyloid beta-Peptides
Contrast Media
Iodine Radioisotopes
Ligands
Peptide Fragments
Radiopharmaceuticals
Thiophenes
amyloid beta-protein (1-42)