BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
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Table 2. In-vitro Aβ42 fibril binding assay and prediction of BBB
penetration for 1a–c, 2a–c, and 3a–c.
Compd. no.
Ki (nM)a at TZ binding sites
In-silico AlogP
1a
1b
1c
2c
3a
3c
0.31
0.42
0.99
0.53
0.70
0.55
0.68
7.035
7.002
7.035
6.002
5.436
5.403
PIB
a Ki was calculated by the Cheng–Prusoff equation [Ki = IC50/(1 + [L]/
Kd)]24 using the Graphpad Prism software.
17. S. R. Byeon, Y. J. Jin, S. J. Lim, J. H. Lee, K. H. Yoo,
K. J. Shin, S. J. Oh, D. J. Kim, Bioorg. Med. Chem. Lett.
2007, 17, 4022.
18. H. J. Lee, S. J. Lim, S. J. Oh, D. H. Moon, D. J. Kim, J. Tae, K. H.
Yoo, Bioorg. Med. Chem. Lett. 2008, 18, 1628.
19. A. K. Bhattacharya, G. Thyagarajan, Chem. Rev. 1981, 81, 415.
20. J. M. Kauffman, G. Moyna, J. Org. Chem. 2003, 68, 839.
21. H. LeVine III., Arch. Biochem. Biophys. 2002, 404, 106 In-vitro.
ThTassay:thefinalconcentrationofAβ42(Bachem, Bubendorf,
Switzerland) was 25 μM. The excitation and emission wave-
lengths were 450 and 482 nm with a 10-nm slit (LS-55 lumines-
cence spectrometer: Perkin-Elmer).
prediction of BBB penetration was accomplished by means of
in-silico AlogP. Most compounds possessed slightly higher
AlogP values (7.0–5.4) than the recommended level
(AlogP ≤ 5).
In conclusion, bis-styrylnaphthalene derivatives 1a–c
showed excellent inhibitory activities of Aβ42 fibril formation
as well as binding affinities to Aβ42 fibrils. These compounds
could be considered as both inhibitors for Aβ42 fibril forma-
tion and ligands for molecular imaging agents in AD brain.
22. We estimated Kd value (0.13 nM) of [125I]TZDM for Aβ42
aggregates. For inhibitionstudies, thereactionmixturecontained
50 μL of Aβ42 aggregates (11.5 nM final conc.), 50 μL of inhi-
bitors (10–6–10–12 M in DMSO), 50 μL of [125I]TZDM (in 40%
EtOH, 0.05 nM in the final conc.), and 10% EtOH in a final vol-
ume of 1 mL. Nonspecific binding was defined by adding 2 μM
Th-T for [125I]TZDM binding. The mixture was incubated at
room temperature for 3 h and the bound and the free radioactivity
were separated by a vacuum filtration through Whatman GF/B
filters using a Brandel M-24R cell harvester followed by 2 × 3
mL washes of 10% EtOH at room temperature. Filters containing
the bound radioligand were counted in a γ-counter (Cobra-II).
The result of inhibition assays was subjected to nonlinear regres-
sion analysis using Graphpad Prism software by which the Ki
values were calculated.
Acknowledgments. This work was funded by the KIST Insti-
tutional Program (Grant No. 2E24760) from the Korea Insti-
tute of Science and Technology, and by the Creative Fusion
Research Program (Grant No. CAP-12-1) from the Korea
Research Council of Fundamental Science and Technology.
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23. Spectroscopic data of target compounds. 1a: 1H NMR (400
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