Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer´s disease therapy

Hiremathad, Asha; Chand, Karam; Tolayan, Lori; RAJESHWARI, .; Keri, Rangappa S.; Esteves, A. Raquel; Cardoso, Sandra M.; Chaves, Sı́lvia; Santos, M. Amélia

doi:10.1016/j.jinorgbio.2017.11.015

Cited by 41 publications

(36 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many Figure 62. Structure of compounds 80 a-c. [150] benzofuran-and indole-based compounds such as melatonin, [130] tacrine-melatonin hybrid 38, [118,119] fluvastatin, [115] compound 39 d, [120] andc lioquinol-moracin Mh ybrid 40 [124] display selectivem ultifunctional activity against AD. To design MTDLs, it is of utmost importance to understand the relationship between b-amyloid oligomers and distinct prion-like structureso r strains and other related factors to develop as uccessful therapy for AD.…”

Section: Discussionmentioning

confidence: 99%

“…Hiremathad et al report al ibrary of (3-hydroxy-4-pyridinone)benzofuran hybrids as inhibitors of AChE and Ab aggregationt hat also show metal chelation and radical-scavenging properties. [150] Amongt he synthesized compounds, 80 a and 80 b/80 c ( Figure 62) show multiple actions by targeting three and four pathophysiological targets of AD, respectively.T he compounds show neuroprotective effects in neuronal cells and evidence good membrane permeability.…”

Section: Benzofuran-and Indole-based Multifunctionalinhibitorsmentioning

confidence: 99%

See 1 more Smart Citation

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

2018

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration has approved drugs (e.g., rivastigmine, donepezil, galantamine, and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Looking at the wide pharmaceutical applications of heterocyclic compounds and particularly those containing benzofuran and indole ring systems, these molecular frameworks have drawn special attention from medicinal chemists for further evaluation in numerous diseases. This article focuses on the history and recent advances of benzofuran- and indole-based compounds as inhibitors of butyrylcholinesterase, acetylcholinesterase, γ-secretase, β-secretase, tau misfolding, and β-amyloid aggregation.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Benzofuran-and Indole-based Multifunctionalinhibitorsmentioning

confidence: 99%

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

2018

View full text Add to dashboard Cite

show abstract

“…However, these exhibited moderate to improved antioxidant properties in comparison with the reference drug deferiprone (174 μ m ). Thus, the presence of methoxy group series improved the antioxidant capacity . Further, Tc AChE enzymatic inhibition properties of the synthesized hybrids 9(a–l) were analysed using the method described in the literature .…”

Section: Resultsmentioning

confidence: 99%

“…This structure was chosen because of the above referred similarity between the original inhibitor (Donepezil) and herein studied ligands, namely between the benzylpiperidine and the indanone moieties of donepezil and corresponding coumarin and benzofuran moieties of the ligands. Further, molecular simulations and docking were performed as previously described method …”

Section: Methodsmentioning

confidence: 99%

“…To deal the several targets of AD simultaneously, we have proposed the dual‐acting multitargeted molecules as anti‐AD agents and accordingly developed the benzofuran (donepezil component known for AChE inhibition) and coumarin (known for the AChE inhibition antioxidant and anti‐Aβ self‐aggregation)‐based hybrids to provide new class of anti‐AD molecules as shown in Figure . The coupling of these two selected pharmacophores was designed through amidic linkage of aliphatic chain and adequate length of alkyl linker was optimized through molecular docking simulations, so that designed molecules can fit comfortably in the cavity of acetylcholinesterase ( Tc AChE) enzyme and provide maximum interaction with catalytic active site (CAS) and the peripheral anionic site (PAS) to induce maximum AChE inhibition.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development of coumarin–benzofuran hybrids as versatile multitargeted compounds for the treatment of Alzheimer’s Disease

2018

Self Cite

View full text Add to dashboard Cite

Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by progressive deterioration of memory and cognition. The evidenced multifactorial nature of AD has been considered the main reason for the absence of cure so far. Therefore, the development of novel hybrids to treat the disease is very much essential. Focusing on this, a novel series of coumarin-benzofuran hybrids have been designed and screened as anti-Alzheimer's disease agents. The strategy is to obtain an effective mimetic of donepezil, which is acetylcholinesterase inhibitor. Herein, the two main scaffolds namely coumarin and benzofuran are known pharmacophore moieties and we have performed their molecular design, pharmacokinetic descriptor studies for drug-likeliness. Further, in vitro studies such as antioxidant capacity, acetylcholinesterase (AChE) inhibition and amyloid-β (Aβ) self-aggregation inhibition have also been performed. Most importantly, these studies revealed that the newly synthesized hybrids can be versatile and promising drug-like moieties as efficient anti-AD agents.

show abstract

Advances in Synthetic Strategies and Medicinal Importance of Benzofurans: A Review

Dwarakanath

Gaonkar

2022

Asian J Org Chem

View full text Add to dashboard Cite

Out of the many heterocycles that exhibit pharmaceutical and therapeutic properties, benzofurans remain the most eye-catching to scientists ever since their discovery. From being present in natural products to synthetic analogs they show diverse biological properties which are used to treat various diseases. Interestingly, some of the benzofuran hybrids were docked against COVID-19 Main Protease and it showed appealing results. Apart from medicinal properties it also exhibits some non-drug applications. The structure activity relationship of benzofuran derivatives in many infections draws attention to the extent where drugs can be produced in a short time span which highlights their significance in medicinal chemistry. There are considerable reaction schemes to synthesize this moiety either simple one pot reactions or multistep. Here, we emphasize on the chemistry of benzofurans, synthesis and its derivatives in the recent years, some of which show notable anti-tumor, antifungal, anti-mycobacterial and anti-oxidant activities.

show abstract

Hydroxypyridinone-benzofuran hybrids with potential protective roles for Alzheimer´s disease therapy

Cited by 41 publications

References 46 publications

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

Development of coumarin–benzofuran hybrids as versatile multitargeted compounds for the treatment of Alzheimer’s Disease

Advances in Synthetic Strategies and Medicinal Importance of Benzofurans: A Review

Contact Info

Product

Resources

About