Cyclodextrin Nanoparticles Bearing 8‐Hydroxyquinoline Ligands as Multifunctional Biomaterials

Oliveri, Valentina; Bellia, Francesco; Vecchio, Graziella

doi:10.1002/chem.201700031

Cited by 28 publications

(24 citation statements)

References 50 publications

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“…[5,6] Among these,p hthalocyanines are the most commonly investigated compounds, [7][8][9] whereas the effect of porphyrins on Ab aggregationa nd toxicity has been less explored. [12,13] We have recently reported that the conjugation of Tre [14,15] and CDs [16][17][18] with aromatic moieties could provide an ew strategy to prevent Ab aggregation. [12,13] We have recently reported that the conjugation of Tre [14,15] and CDs [16][17][18] with aromatic moieties could provide an ew strategy to prevent Ab aggregation.…”

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confidence: 99%

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Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity

Oliveri

Zimbone

Giuffrida

et al. 2018

Chemistry A European J

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Although fibrillara myloid beta peptide( A b)a ggregates are one of the major hallmarks of Alzheimer's disease, increasing evidences uggeststhat soluble Ab oligomers are the primaryt oxic species. Ta rgeting the oligomeric speciesc ould represent an effective strategy to interfere with Ab toxicity. In this work, the biological properties of 5[4-(6-O-b-cyclodextrin)-phenyl],10,15,20-tri(4-hydroxyphenyl)-porphyrina nd its zinc complex were tested, as new molecules that interactw ith Ab and effectively preventi ts cytotoxicity.W ef ound that these systems can cross the cell membrane to deliver Ab intracellularlya nd promote its clearance. Our resultsp rovide evidencef or the use of cyclodextrin-porphyrin derivatives as ap romising strategy to target amyloid aggregation.The amyloid beta peptide( A b)h as been implicated as am ajor component in the development of Alzheimer's disease (AD). Much efforth as therefore been made to investigate the compositiono fa myloid plaques, the mechanism underlying Ab fibril formation,a nd the parameters that could contribute to the Ab toxicity. Although fibrillar Ab aggregates are one of the major hallmarks of AD, increasing evidence suggestst hat soluble oligomers of the peptide are the primary toxic species. [1] The structure and formation of Ab oligomers have been largely investigated. However,t he interplay between conformation and size in determining their toxicityi sstill underd ebate.It has been reported that soluble Ab oligomers are organized into different structures ranging from dimers to dodecamers, Ab*56, [2] and Ab-derived diffusible ligands(ADDLs). [3] Therefore, targeting one of theset oxic oligomeric species could represent an effective strategy to interferew ith Ab toxicity. [4] Several small molecules, including tetrapyrrolic compounds, have been reported to modulate the amyloid aggregation of several proteins, such as tau, Ab,a nd a-synuclein. [5,6] Among these,p hthalocyanines are the most commonly investigated compounds, [7][8][9] whereas the effect of porphyrins on Ab aggregationa nd toxicity has been less explored. [10,11] Moreover,n umerous studies have also shown that sugars such as trehalose (Tre) and cyclodextrins (CDs)m ay be protectivea gainst neuronal degeneration observed in AD. [12,13] We have recently reported that the conjugation of Tre [14,15] and CDs [16][17][18] with aromatic moieties could provide an ew strategy to prevent Ab aggregation.Herein, we show that a bCD derivativeb earing ap orphyrin moiety 5[4-(6-O-b-cyclodextrin)-phenyl],10,15,20-tri(4-hydroxyphenyl)-porphyrin (CDTHPP,F igure 1A and Figure S1 in the Supporting Information) is effective in inhibiting Ab 42 cytotoxicity.C ontrarily, bCD is not effective, and THPP is toxic. We also report the synthesis of the Zn complex of CDTHPP (ZnCDTHPP), that was studiedt ot est the effect of the metali n modulating the biological properties of the conjugate CDTHPP. Moreover,w ei nvestigated in parallel the activity of bCD or 5,10,15,20-tetra(4-hydroxyphenyl)-porphyrin (THPP).First, we studied th...

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“…[10,11] Moreover,n umerous studies have also shown that sugars such as trehalose (Tre) and cyclodextrins (CDs)m ay be protectivea gainst neuronal degeneration observed in AD. [12,13] We have recently reported that the conjugation of Tre [14,15] and CDs [16][17][18] with aromatic moieties could provide an ew strategy to prevent Ab aggregation.…”

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confidence: 99%

Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity

Oliveri

Zimbone

Giuffrida

et al. 2018

Chemistry A European J

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“…Competitive binding experiments were run to reveal the binding site of compounds on HSA, with hemin, subdomain IB marker, which specifically bind to HSA . Typically, the effect of addition of Cu (II) complex to HSA‐hemin solution on its absorption spectrum has been illustrated in Figure .…”

Section: Resultsmentioning

confidence: 99%

New transition metal complexes of 9,10‐phenanthrenequinone p‐toluyl hydrazone Schiff base: Synthesis, spectroscopy, DNA and HSA interactions, antimicrobial, DFT and docking studies

Moradinia

Mansournia

Aramesh‐Boroujeni

et al. 2019

Applied Organom Chemis

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The new complexes of Cu (II) and Ni (II) of a tridentate Schiff base ligand derived from 9,10‐phenanthrenequinone and p‐toluic hydrazide have been synthesized and characterized by elemental analysis, electrical conductometry, FT‐IR, Mass, NMR and UV–Vis. The DFT calculations were carried out at B3LYP/6‐31G*(d) level for the determination of the optimized structure of the ligand and its complexes. The as‐synthesized compounds were screened for their antimicrobial activity. Also, their binding behavior with fish salmon‐DNA (FS‐DNA) and human serum albumin (HSA) were studied by different kinds of spectroscopic and molecular modeling techniques. The fluorescence data at different temperatures were applied in order to estimate the thermodynamics parameters of interactions of ligand and its complexes with DNA and HSA. The results showed that the as‐made compounds could bind to FS‐DNA and HSA via the groove binding as the major binding mode. According to molecular docking calculation and competitive binding experiments, these compounds bind to the minor groove of DNA and hydrophobic residues located in the subdomain IB of HSA. In addition, the molecular docking results kept in good consistence with experimental data.

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“…We previously conjugated metal chelators such as deferiprone and clioquinol with β‐cyclodextrin (CyD) . Studies on these conjugates indicated that CyD conjugation improves some features of the chelators and makes them multifunctional . CyDs have been studied as artificial chaperones and anti‐aggregant agents .…”

Section: Introductionmentioning

confidence: 99%

“…[12,13] Studies on these conjugates indicated that CyD conjugation improves some features of the chelators and makes them multifunctional. [14,15] CyDs have been studied as artificial chaperones and anti-aggregant agents. [16,17] Methyl-b-CyD has been reported to reduce a-synuclein (aSyn) accumulation, ap rotein implicated in Parkinson's disease (PD).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Study of Multifunctional Cyclodextrin–Deferasirox Hybrids

et al. 2019

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Metal dyshomeostasis is central to a number of disorders that result from, inter alia, oxidative stress, protein misfolding, and cholesterol dyshomeostasis. In this respect, metal deficiencies are usually readily corrected by treatment with supplements, whereas metal overload can be overcome by the use of metal‐selective chelation therapy. Deferasirox, 4‐[(3Z,5E)‐3,5‐bis(6‐oxo‐1‐cyclohexa‐2,4‐dienylidene)‐1,2,4‐triazolidin‐1‐yl]benzoic acid, Exjade, or ICL670, is used clinically to treat hemosiderosis (iron overload), which often results from multiple blood transfusions. Cyclodextrins are cyclic glucose units that are extensively used in the pharmaceutical industry as formulating agents as well as for encapsulating hydrophobic molecules such as in the treatment of Niemann–Pick type C or for hypervitaminosis. We conjugated deferasirox, via an amide coupling reaction, to both 6A‐amino‐6A‐deoxy‐β‐cyclodextrin and 3A‐amino‐3A‐deoxy‐2A(S),3A(S)‐β‐cyclodextrin, at the upper and lower rim, respectively, creating hybrid molecules with dual properties, capable of both metal chelation and cholesterol encapsulation. Our findings emphasize the importance of the conjugation of β‐cyclodextrin with deferasirox to significantly improve the biological properties and to decrease the cytotoxicity of this drug.

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Cyclodextrin Nanoparticles Bearing 8‐Hydroxyquinoline Ligands as Multifunctional Biomaterials

Cited by 28 publications

References 50 publications

Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity

Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity

New transition metal complexes of 9,10‐phenanthrenequinone p‐toluyl hydrazone Schiff base: Synthesis, spectroscopy, DNA and HSA interactions, antimicrobial, DFT and docking studies

Synthesis and Study of Multifunctional Cyclodextrin–Deferasirox Hybrids

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