Investigation of the photostability properties of memoquin, a quinone derivative for the treatment of Alzheimer's disease

Mancini, Francesca; Bolognesi, María Laura; Melchiorre, Carlo; Andrisano, Vincenza

doi:10.1016/j.jpba.2009.04.017

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…A study of the photo-stability properties of memoquin indicates that it has two photo-reactive centers within the amino groups of its side chains. The functionality and stability of the 1,4-benzoquinone pharmacophore suggested potential use of memoquin as a stable and active anti-AD drug [92]. Tacrine-melatonin hybrids have already been described in several papers.…”

Section: Hybrid Ache/buche Inhibitors With Antioxidant and Neuroprotementioning

confidence: 99%

“…Performance improvements in a variety of animal memory models have been described for CB 1 receptor antagonists as well as for combined administration of the CB 1 receptor antagonist rimonabant and donepezil [123]. Novel hybrid molecules have been designed by connecting a tacrine structure with 3,4-diarylpyrazoline or 1,2-diarylimidazole pharmacophores, characteristic of CB 1 receptor antagonists (91,92), using an alkyl spacer (Fig. 32).…”

Section: Hybrid Ache Inhibitors With Cannabinoid Cb 1 Receptor Antagomentioning

confidence: 99%

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Multi-Target-Directed Ligands in Alzheimer's Disease Treatment

Bajda

Guzior²,

Ignasik³

et al. 2011

CMC

220

131

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Among the various drug discovery methods, a very promising modern approach consists in designing multi-target-directed ligands (MTDLs). This methodology has been specifically developed for treatment of disorders with complex pathological mechanisms. One such disorder is Alzheimer's disease (AD), currently the most common multifactorial neurodegenerative disease. AD is related to increased levels of the amyloid β peptide (Aβ) and the hyperphosphorylated tau protein, along with loss of neurons and synapses. Moreover, there is some evidence pointing to the role of oxidative stress, metal ion deregulation, inflammation and cell cycle regulatory failure in its pathogenesis. There are many attractive targets for the development of anti-AD drugs, and the multi-factor nature of this disease calls for multi-target-directed compounds which can be beneficial for AD treatment. This review presents the discovery of dualand multi-acting anti-AD drug candidates, focusing on the novel design strategy and the compounds it yields - particularly hybrids obtained by linking structurally active moieties interacting with different targets. The first group of compounds includes cholinesterase inhibitors acting as dual binding site inhibitors and/or inhibitors with additional properties. These compounds are characterized by increased potency against acetylcholinesterase (AChE) and Aβ plaque formation with additional properties such as antioxidant activity, neuroprotective, and metal-complexing property, voltage-dependent calcium channel antagonistic activity, inhibitory activity against glutamate-induced excitotoxicity, histamine H(3) receptor antagonism, cannabinoid CB(1) receptor antagonism and β-secretase (BACE1) inhibition. A novel class of compounds represents the combination of dual BACE1 inhibitors with metal chelators, and dual modulators of γ-secretase with peroxisome proliferator-ativated receptor γ (PPARγ). We have reviewed the latest reports (2008-2011) presenting new multi-target-directed compounds in Alzheimer's disease treatment.

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Section: Hybrid Ache/buche Inhibitors With Antioxidant and Neuroprotementioning

confidence: 99%

Section: Hybrid Ache Inhibitors With Cannabinoid Cb 1 Receptor Antagomentioning

confidence: 99%

Multi-Target-Directed Ligands in Alzheimer's Disease Treatment

Bajda

Guzior²,

Ignasik³

et al. 2011

CMC

220

131

View full text Add to dashboard Cite

show abstract

Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils

Giménez¹,

Rincón²,

Jiménez-Aliaga³

et al. 2011

Bioorganic & Medicinal Chemistry Letters

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Discovery of Multi-Target Agents for Neurological Diseases via Ligand Design

Bolognesi

Melchiorre

Schyf

et al. 2012

Designing Multi-Target Drugs

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The incidence of neurological disorders in the developed world is rising in concert with an increase in human life expectancy, due in large part to better nutrition and health care. Even as drug discovery efforts are refocused on these disorders, there has been a dearth in the introduction of new disease-modifying therapies to prevent or delay their onset, or reverse their progression. Mounting evidence points to complex and heterogeneous etiopathologies that underlie these diseases. Therefore, it is unlikely that disorders in this class will be mitigated by any single drug that acts exclusively on a single pathway or target. The rational design of novel drug entities with the ability to simultaneously address multiple drug targets of a complex pathophysiology has recently emerged as a new paradigm in drug discovery. Similarly to the concept of multi-target agents within the psychopharmacology field, ligand design has gained an increasing prominence within the medicinal chemistry community. In this chapter we discuss several examples of select chemical scaffolds (polyamines, alkylxanthines, and propargyl carbamates) wherein these concepts were applied to develop novel drug candidates for Alzheimer's disease and Parkinson's disease.

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Investigation of the photostability properties of memoquin, a quinone derivative for the treatment of Alzheimer's disease

Cited by 4 publications

References 18 publications

Multi-Target-Directed Ligands in Alzheimer's Disease Treatment

Multi-Target-Directed Ligands in Alzheimer's Disease Treatment

Synthesis and evaluation of arylquinones as BACE1 inhibitors, β-amyloid peptide aggregation inhibitors, and destabilizers of preformed β-amyloid fibrils

Discovery of Multi-Target Agents for Neurological Diseases via Ligand Design

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