Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer's disease

Dias, Kris Simone Tranches; Paula, Cynthia T. de; Santos, Thiago dos; Souza, Isis N. O.; Boni, Marina S.; Guimarães, Marcos Jorge R.; Silva, Fernanda M.R. da; Castro, Newton G.; Neves, Gilda; Veloso, Clarice C.; Coelho, Márcio M.; Melo, Ivo S.F.; Vilela, Fabiana C.; Giusti‐Paiva, Alexandre; Silva, Marcelo L. da; Dardenne, Laurent E.; Guedes, Isabella Alvim; Pruccoli, Letizia; Morroni, Fabiana; Tarozzi, Andrea; Viegas, Cláudio

doi:10.1016/j.ejmech.2017.02.043

Cited by 72 publications

(31 citation statements)

References 68 publications

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“…40 We would like note that all the biological activities observed with our most active compounds are within the same range of activities reported by others working in similar field. [41][42][43] Conclusions A series of vanillin derivatives was synthesized and found to have similar antioxidant activity to the reference antioxidant, Trolox, except for compound 1. The results obtained in antioxidant assays agree with our previous study regarding the structure activity relationship for this class of antioxidants.…”

Section: Inhibition Of Self-mediated Aβ (1-42) Aggregationmentioning

confidence: 94%

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

et al. 2019

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Section: Inhibition Of Self-mediated Aβ (1-42) Aggregationmentioning

confidence: 94%

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

et al. 2019

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“…Feruloyl-donepezil hybrids were developed as another example of novel and potent MTDLs 102 . Variation of the substituent groups in the aromatic region of N -benzylpiperidine derived from donepezil as well as aromatic part of feruloyl were explored in the effort to identify novel drug candidate.…”

Section: Donepezil Derivatives With Antioxidant Propertiesmentioning

confidence: 99%

Profiling donepezil template into multipotent hybrids with antioxidant properties

Mezeiová

Špilovská

Nepovimová

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Alzheimer’s disease is debilitating neurodegenerative disorder in the elderly. Current therapy relies on administration of acetylcholinesterase inhibitors (AChEIs) -donepezil, rivastigmine, galantamine, and N-methyl-d-aspartate receptor antagonist memantine. However, their therapeutic effect is only short-term and stabilizes cognitive functions for up to 2 years. Given this drawback together with other pathological hallmarks of the disease taken into consideration, novel approaches have recently emerged to better cope with AD onset or its progression. One such strategy implies broadening the biological profile of AChEIs into so-called multi-target directed ligands (MTDLs). In this review article, we made comprehensive literature survey emphasising on donepezil template which was structurally converted into plethora of MTLDs preserving anti-cholinesterase effect and, at the same time, escalating the anti-oxidant potential, which was reported as a crucial role in the pathogenesis of the Alzheimer’s disease.

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“…Initially, all compounds were screened at a standard screening concentration of 30 μM and the resulting percentages of AChE inhibition by the triazole derivatives 3a – m are shown in Figure 3 . Compound 3e was identified as the most active in the series, inhibiting more than 50% of the AChE activity at the screening concentration and exhibiting an IC 50 value of 26.30 μM, being more potent than curcumin (IC 50 = 132.13 μM [ 26 ]), but less potent than donepezil (IC 50= 0.026 μM [ 26 ]). A study was also performed to verify the ability of 3e to inhibit BuChE, but no relevant activity was detected, being selective against AChE.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease

et al. 2020

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Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics.

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Design, synthesis and evaluation of novel feruloyl-donepezil hybrids as potential multitarget drugs for the treatment of Alzheimer's disease

Cited by 72 publications

References 68 publications

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

Synthesis of novel vanillin derivatives: novel multi-targeted scaffold ligands against Alzheimer's disease

Profiling donepezil template into multipotent hybrids with antioxidant properties

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer’s Disease

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