Timely detection of amyloid aggregations has a critical role in the treatment of degenerative nervous system disorders such as Alzheimer’s, Parkinson’s disease and systemic amyloidosis. Thioflavin T (ThT) is a dye considered for the detection of amyloids. However, ThT cannot cross the blood–barrier barrier due to positive charge and low lipophilicity. In the present study, a variety of 2-benzylidene-1,3-indandione derivatives 5a–5j were synthesized as neutral fluorescence probe candidates for identification of amyloid. Among these compounds, only compound 2-(2-hydroxybenzylidene)-1,3-indandione 5a was selected for further examination, because its fluorescence intensity showed the significant increasing upon interaction with amyloid aggregates. The compound 5a was compared to standard and conventional probe such as ThT. The compound 5a was excited at its specified wavelength, and the fluorescence emission signal was recorded in the presence of different concentrations of the protein/peptide (amyloid aggregated and native protein). According to the obtained results, it can be seen that 2-(2-hydroxybenzylidene)-1,3-indandione 5a selectively and specifically bind to amyloid fibrils, such as ThT. Due to the neutrality of electrical charge and high lipophilicity coefficient of the synthesized compound 5a, it is possible for it to cross from the blood–brain barrier. Our results show that this synthetic derivative can be considered as a suitable probe to detect in vitro amyloid aggregations.
This is a preview of subscription content, log in to check access.
Buy single article
Instant unlimited access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
G. Bhak, Y.J. Choe, S.R. Paik, BMB Rep. 42, 541 (2009)
S. Babri, G. Mohaddes, I. Feizi, A. Mohammadnia, A. Niapour, A. Alihemmati et al., Eur. J. Pharmacol. 732, 19 (2014)
D.R. Borchelt, T. Ratovitski, J. Van Lare, M.K. Lee, V. Gonzales, N.A. Jenkins et al., Neuron 19, 939 (1997)
M. Landau, M.R. Sawaya, K.F. Faull, A. Laganowsky, L. Jiang, S.A. Sievers, J. Liu, J.R. Barrio, D. Eisenberg, PLoS Biol. 9, e1001080 (2011)
B. Bulic, M. Pickhardt, B. Schmidt, E.M. Mandelkow, H. Waldmann, E. Mandelkow, Angew. Chem. Int. Ed. Engl. 48, 1740 (2009)
A. Jangholi, M.R. Ashrafi-Kooshk, S.S. Arab, G. Riazi, F. Mokhtari, M. Poorebrahim, H. Mahdiuni, B.I. Kurganov, A.A. Moosavi-Movahedi, R. Khodarahmi, Archiv. Biochem. Biophys. 609, 1 (2016)
W.J. Goux, L. Kopplin, A.D. Nguyen, K. Leak, M. Rutkofsky, V.D. Shanmuganandam, D. Sharma, H. Inouye, D.A. Kirschner, J. Biol. Chem. 279, 26868 (2004)
N. Bijari, S. Balalaie, V. Akbari, F. Golmohammadi, S. Moradi, H. Adibi, R. Khodarahmi, Int. J. Biol. Macromol. 120, 1009 (2018)
V.N. Uversky, A.L. Fink, BBA Proteins Proteom. 1698, 131 (2004)
M. Biancalana, K. Makabe, A. Koide, S. Koide, J. Mol. Biol. 385, 1052 (2009)
E. Voropai, M. Samtsov, K. Kaplevskii, A. Maskevich, V. Stepuro, O. Povarova et al., J Appl. Spectrosc. 70, 868 (2003)
S.A. Hudson, H. Ecroyd, T.W. Kee, J.A. Carver, FEBS J. 276, 5960 (2009)
M.D. Kirkitadze, A. Kowalska, Acta Biochim. Polon. 52, 417 (2005)
N. Darghal, A. Garnier-Suillerot, M. Salerno, Biochem. Biophys. Res. Commun. 343, 623 (2006)
S. Abbasbreigi, H. Adibi, S. Moradi, S.A. Ghadami, R. Khodarahmi, J Iran. Chem. Soc. 16, 1225–1237 (2019)
S.A. Ghadami, Z. Hossein-pour, R. Khodarahmi, S. Ghobadi, H. Adibi, Med. Chem. Res. 22, 115–126 (2013)
F.A. Rojas Quijano, D. Morrow, B.M. Wise, F.L. Brancia, W.J. Goux, Biochemistry 45, 4638 (2006)
W. Dzwolak, M. Pecul, FEBS Lett. 579, 6601 (2005)
A. Loksztejn, W. Dzwolak, J. Mol. Biol. 379, 9 (2008)
M. Biancalana, S. Koide, Biochim. Biophys. Acta 1804, 1405 (2010)
M.R. Krebs, E.H. Bromley, A.M. Donald, J. Struct. Biol. 149, 30 (2005)
J.H. Cooper, Lab. Invest. 31, 232 (1974)
L.W. Jin, K.A. Claborn, M. Kurimoto, M.A. Geday, I. Maezawa, F. Sohraby, M. Estrada, W. Kaminksy, B. Kahr, Proc. Natl. Acad. Sci. USA 100, 15294 (2003)
We gratefully acknowledge Vice Chancellery for Research and Technology, Kermanshah University of Medical Sciences for financial support (Grant No. 93209). This article resulted from the Pharm.D thesis of Kazhal Amiri, major of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
About this article
Cite this article
Adibi, H., Mehrabi, M., Amiri, K. et al. Synthesis and characterization of 2-benzylidene-1,3-indandione derivatives as in vitro quantification of amyloid fibrils. J IRAN CHEM SOC 17, 423–432 (2020) doi:10.1007/s13738-019-01776-2
- Amyloid aggregation
- Alzheimer’s disease (AD)
- Indanone derivatives
- Thioflavin T (ThT)
- β-Amyloid plaques