Structural Isomers of Cyclodextrin‐Bearing IOX1 Compound as Inhibitors of Aβ Aggregation

Oliveri, Valentina; Bellia, Francesco; Vecchio, Graziella

doi:10.1002/slct.201601651

Cited by 10 publications

(10 citation statements)

References 31 publications

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“…First, the aggregation process of Aβ was monitored by dynamic light scattering (DLS, Figure S11). The formation of aggregates was observed when Aβ is incubated at 37 °C (pH 7.4) for 24–48 h. The freshly prepared Aβ sample (t=0 h) showed no signal or a profile of small‐sized aggregates as previously observed elsewhere …”

Section: Resultssupporting

confidence: 65%

Synthesis and Evaluation of New Cyclodextrin Derivatives as Amyloid‐β Aggregation Inhibitors

Oliveri

Vecchio

2019

ChemistrySelect

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The presence of extracellular amyloid‐beta (Aβ) plaques is one of the pathological hallmarks of Alzheimer's disease. Appropriately functionalized compounds can modulate amyloidogenesis. Here, we report a new class of cyclodextrin (CyD) derivatives rationally designed to improve the Aβ recognition and to modulate its aggregation. In particular, a dimethylamino aromatic moiety was conjugated to βCyD or γCyD to explore how different structural aspects of these derivatives could influence the recognition and the aggregation of Aβ. The conjugation of the Aβ recognition moiety to CyDs resulted in a significant suppression of the self‐assembly propensity of Aβ when the dimethylamino aromatic moiety was attached to the upper rim of βCyD. The activity of the derivatives toward Aβ confirms that the conjugation of CyDs with Aβ recognition moieties may be considered a promising approach for designing new molecules that interfere with Aβ aggregation.

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Section: Resultssupporting

confidence: 65%

Synthesis and Evaluation of New Cyclodextrin Derivatives as Amyloid‐β Aggregation Inhibitors

Oliveri

Vecchio

2019

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“…Vecchio et al synthesized a variety of β-CD derivatives and evaluated their effects on the aggregation of Aβ 1-42 . CD-5-carboxy-8-hydroxyquinoline (IOX) (5-carboxy-8hydroxyquinoline) [87] and CD-dimethylamminobenzene [88] exert better inhibitory effects than β-CD (1:5, Aβ:CD derivatives). The conjugate of porphyrin with β-CD (CDTHPP) effectively decreases the cytotoxicity of Aβ 1-42 (1:1, Aβ:CDTHPP).…”

Section: Cdsmentioning

confidence: 99%

Modulating the aggregation of amyloid proteins by macrocycles

2022

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The aggregation of amyloid proteins has been suggested to be the main cause of multiple human disorders; for example, amyloid β aggregates in Alzheimer's disease and α-synuclein aggregates in Parkinson's disease. In the search for therapeutic medicines, many molecules have been discovered and developed to modulate the aggregation of amyloid proteins. This century has witnessed the flourishing growth of supramolecular chemistry, and some biocompatible macrocycles have been proven to inhibit the aggregation of some amyloid proteins via host-guest interactions and could thus be used for the prevention or treatment of related diseases. Here, we review the application of macrocycles in modulating the aggregation of amyloid proteins.

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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%

“…[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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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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Structural Isomers of Cyclodextrin‐Bearing IOX1 Compound as Inhibitors of Aβ Aggregation

Cited by 10 publications

References 31 publications

Synthesis and Evaluation of New Cyclodextrin Derivatives as Amyloid‐β Aggregation Inhibitors

Synthesis and Evaluation of New Cyclodextrin Derivatives as Amyloid‐β Aggregation Inhibitors

Modulating the aggregation of amyloid proteins by macrocycles

Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity

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