New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol

Mao, Fei; Yan, Jun; Li, Jianheng; Jia, Xian; Miao, Hui; Sun, Yang; Huang, Ling; Li, Xingshu

doi:10.1039/c4ob00998c

Cited by 91 publications

(72 citation statements)

References 42 publications

(40 reference statements)

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“…Orcein was found to bind parallel to the long axis of Ab42 aggregates targeting the hydrophobic region of spherical oligomeric Ab42 species. 109 Inhibitor 17 showed higher inhibition and dissolution efficiency for copperguided Ab42 aggregates, antioxidant properties and BBB permeability compared to its constituent elements clioquinol and resveratrol. 104 Brazilin (15), a natural product obtained from Caesalpinia sappan, inhibited Ab42 aggregation and also remodeled Ab42 aggregates to prevent them from acting as secondary nucleation centers for further fibrillogenesis.…”

Section: View Article Onlinementioning

confidence: 96%

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

2015

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Amyloidogenesis has been implicated in a broad spectrum of diseases in which amyloid protein is invariably misfolded and deposited in cells and organs. Alzheimer's disease is one of the most devastating ailments among amyloidogenesis induced dementia. The amyloid beta (Aβ) peptide derived from amyloid precursor protein (APP) is misfolded and deposited as plaques in the brain, which are said to be the hallmark of Alzheimer's disease. In normal brains physiological concentration of the Aβ peptide has been indicated to be involved in modulating neurogenesis and synaptic plasticity. However, excess Aβ production, its aggregation and deposition deleteriously affect a large number of biologically important pathways leading to neuronal cell death. Targeting Aβ production, Aβ aggregation or its clearance from the brain has been an active area of research for preventing or curing AD. Our Feature Article intends to detail the aggregation mechanism, the physiological role of the Aβ peptide, elaborate its toxic effects, and outline the different classes of molecules designed in the last two years to inhibit amyloidogenic APP processing, Aβ oligomerization or fibrillogenesis and to modulate different pathways for active clearance of Aβ from the brain.

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Section: View Article Onlinementioning

confidence: 96%

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

2015

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“…In the last decades, the interest for derivatives of 8-hydroxyquinoline (8HQ) or 8-quinolinol (1, Figure 1) has increased since they have presented several biological activities such as antibacterial, antifungal, antioxidant, antiviral, and antiparasitic (Cherdtrakulkiat et al, 2016;Kadri, Crater, Lee, Solomon, & Ananvoranich, 2014;Kassem et al, 2012;Li et al, 2017;Oliveri & Vecchio, 2016;Zuo et al, 2016). Recent studies also show that 8HQ derivatives are promising for the development of therapies for diseases such as Alzheimer's, Parkinson's, Huntington's, as well as neoplasms (Bareggi & Cornelli, 2012;Chen et al, 2007;Fu, Hsu, Liao, & Hu, 2016;Kubanik, Holtkamp, Söhnel, Jamieson, & Hartinger, 2015;Mao et al, 2014;Nguyen, Hamby, & Massa, 2005).…”

Section: Introductionmentioning

confidence: 99%

Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines

et al. 2018

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The combination of tools such as time‐kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8‐hydroxy‐5‐quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8‐hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time‐kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC50 values obtained by combination of time‐kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non‐irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.

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“…Nonetheless, three antiviral agents that inhibit HSV1 DNA replication, including acyclovir (ACV), were found to reduce greatly the level of Ab as well as P-tau, with the former probably through prevention of viral spread . Previous studies showed that HSV1 DNA is present and is active in the brain of many elderly people, including AD patients, and that in combination with the type 4 allele of the apolipoprotein E gene, it is likely to play a role in the disease, perhaps via Ab and Ptau production (Mao et al, 2014a) . With the aim of finding the most suitable antiviral for inhibiting Ab and P-tau formation as well as HSV1 DNA replication for future use in a clinical trial for treating AD, Wozniak et al compared the efficacy of ACV with that of another antiviral, BAY 57-1293, which acts by a different mechanism from ACV.…”

Section: Alzheimer's Disease Treatment With Small Molecule β-Amyloid mentioning

confidence: 99%

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

2020

Int. J. Adv. Biol. Biomed. Res.

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Alzheimer's disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. It is a neurodegenerative type of dementia, the disease starts mild and gets progressively worse. Like all types of dementia, Alzheimer's is caused by brain cell death. The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most prominent, especially in the area of learning and recalling new information. Alzheimer's disease is not simple to diagnose for which there is no single test. For this reason, the first thing doctors do is to rule out other problems before confirming whether mental signs and symptoms are severe enough to be a kind of dementia or something else. Genetic test is possible in some settings to indicate the likelihood of someone having or developing the disease but this is controversial and not entirely reliable. There are no disease-modifying drugs available for Alzheimer's disease but some options may reduce its symptoms and help improve quality of life. A different kind of drug, namely memantine, an NMDA receptor antagonist, may also be used, alone or in combination with a cholinesterase inhibitor. This review highlights the several reports that attempt to design and synthesis of some classes of selective Alzheimer's disease inhibitors.

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New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol

Cited by 91 publications

References 42 publications

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines

The recent development in synthesis and pharmacological evaluation of small molecule to treat Alzheimer's diseases: A review

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