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Synthesis and characterization of 2-benzylidene-1,3-indandione derivatives as in vitro quantification of amyloid fibrils

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Abstract

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 5a5j 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.

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Acknowledgements

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.

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Correspondence to Reza Khodarahmi.

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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

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Keywords

  • Amyloid aggregation
  • Alzheimer’s disease (AD)
  • Indanone derivatives
  • Thioflavin T (ThT)
  • β-Amyloid plaques