- Development of dual functional SPECT/fluorescent probes for imaging cerebral β-amyloid plaques
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The imaging of β-amyloid (Aβ) aggregates in the brain may lead to the early detection of Alzheimer's disease (AD) and monitoring of the progression and effectiveness of treatment. The purpose of this study was to develop dual modality SPECT and fluorescent probes based on boron dipyrromethane (BODIPY) as a core structure. We designed and synthesized an 125I-labeled derivative of BODIPY (BODIPY7). BODIPY7 had a K i value of 108 nM for Aβ(1-42) aggregates and exhibited peaks of absorption/emission at 606/613 nm. It detected Aβ plaques in sections of brain tissue from an animal model of AD and displayed low uptake in the brain and high uptake in the liver in normal mice. Although additional modifications of the BODIPY scaffold are necessary to improve brain uptake, these results should aid the development of dual functional SPECT/fluorescent probes for the imaging of Aβ plaques in the brain.
- Ono, Masahiro,Ishikawa, Manami,Kimura, Hiroyuki,Hayashi, Shun,Matsumura, Kenji,Watanabe, Hiroyuki,Shimizu, Yoichi,Cheng, Yan,Cui, Mengchao,Kawashima, Hidekazu,Saji, Hideo
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supporting information; experimental part
p. 3885 - 3888
(2010/09/03)
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- Synthesis and structure-activity relationships of 5-phenylthiophenecarboxylic acid derivatives as antirheumatic agents
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5-(Phenylthiophene)-3-carboxylic acid (2a), a metabolite of esonarimod (1), which was developed as a new antirheumatic drug, was considered as a lead compound for new antirheumatic drugs. A new series of 2a derivatives were synthesized and their characteristic pharmacological effects, that is their antagonistic effect toward interleukin (IL)-1 in mice and the suppressive effect against adjuvant-induced arthritis (AIA) in rats, were evaluated and compared with those of 1. The structure-activity relationships indicated that [5-(4-bromophenyl)-thiophen-3-yl]acetic acid (5d), methyl [5-(4-chlorophenyl)-thiophen-3-yl]acetate (5h), and methyl [5-(4-bromophenyl)-thiophen-3-yl]acetate (5i) suppressed AIA more potently than 1 and all of the other synthesized compounds.
- Noguchi, Toshiya,Hasegawa, Masahiro,Tomisawa, Kazuyuki,Mitsukuchi, Morihiro
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p. 4729 - 4742
(2007/10/03)
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