TY - JOUR
T1 - Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation
AU - Rana, Monika
AU - Cho, Hong Jun
AU - Roy, Tapta Kanchan
AU - Mirica, Liviu M.
AU - Sharma, Anuj K.
N1 - AKS acknowledge Science and Engineering Research Board for financial support (grant ref.: EMR/2016/001452) and DST-INSPIRE research grant (IFA-13, CH-97). MR acknowledges Central University of Rajasthan for fellowship. AKS is thankful to Dr. Jaykant Yadav for helping with amyloid preparation. TKR thanks to Prof. R. T. Pardasani, CU Rajasthan; CMSD, University of Hyderabad for computational support and Central University of Jammu for the infrastructural facilities and for supporting this work through grant CUJ/Acad/Proj-PHY/2017/97. L.M.M. acknowledges research funding from NIH (R01GM114588) and the Alzheimer’s Association (NIRG 12-259199). AKS is DST-INSPIRE faculty awardee. The paper is dedicated to the memories of Dr. Sunil G. Naik.
PY - 2018/2/24
Y1 - 2018/2/24
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ica.2017.11.029
DO - 10.1016/j.ica.2017.11.029
M3 - Article
C2 - 30344337
AN - SCOPUS:85035814344
SN - 0020-1693
VL - 471
SP - 419
EP - 429
JO - Inorganica Chimica Acta
JF - Inorganica Chimica Acta
ER -