Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation

Monika Rana, Hong Jun Cho, Tapta Kanchan Roy, Liviu M. Mirica, Anuj K. Sharma

Research output: Contribution to journalArticle

Abstract

Chemical tools are needed to discover new effective drugs for tackling multifaceted complex neurodegenerative diseases like Alzheimer's disease (AD). Multifunctional nature of two compounds, 5-((4-nitrophenyl)diazenyl)quinolin-8-ol (HL1) and 4-((4-nitrophenyl)diazenyl)benzene-1,3-diol (HL2) is reported w.r.t. their ability to bind Cu2+ ions and amyloid aggregates related to AD. HL1 and HL2 have half congo-red type azo-stilbene structural framework incorporated with metal chelating groups, designed to chelate metal ions from metal-amyloid species. Metal binding studies of HL1 and HL2 are established by the methods of Job's Plot, UV-vis spectra with metal ions and stability constant determination. In addition, their metal complexes are isolated, purity checked by elemental analysis, spectroscopically characterized and their structural analyses were obtained from DFT based calculations including binding energy determination. Chicken egg white Lysozyme (CEWL) was used as a model peptide for fibrillation studies. HL1 is found as an excellent colorimetric sensor for amyloid fibrils. Inhibitory effect of HL1 and HL2 and their isolated metal complexes L1-Cu and L2-Cu on CEWL fibrillation was studied using ThT and ANS fluorescence assay along with TEM imaging. In addition, the cell toxicity studies on these compounds suggest that although azo dyes may be non-toxic but having a nitro-substitution lead to significant cell toxicity. Overall, these results suggest that this new class of multifunctional small molecules can interact with amyloids as well as metal ions and could be potential anti-aggregation metal chelating agents.

Original languageEnglish (US)
Pages (from-to)419-429
Number of pages11
JournalInorganica Chimica Acta
Volume471
DOIs
StatePublished - Feb 24 2018

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Azo Compounds
chelation
Azo dyes
Chelation
Amyloid
dyes
Metals
Metal ions
Molecules
Coordination Complexes
Muramidase
Metal complexes
metals
fibrillation
Toxicity
molecules
metal ions
chickens
Enzymes
eggs

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry
  • Materials Chemistry

Cite this

Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation. / Rana, Monika; Cho, Hong Jun; Roy, Tapta Kanchan; Mirica, Liviu M.; Sharma, Anuj K.

In: Inorganica Chimica Acta, Vol. 471, 24.02.2018, p. 419-429.

Research output: Contribution to journalArticle

Rana, Monika ; Cho, Hong Jun ; Roy, Tapta Kanchan ; Mirica, Liviu M. ; Sharma, Anuj K. / Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation. In: Inorganica Chimica Acta. 2018 ; Vol. 471. pp. 419-429.
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