Evaluation of chromane derivatives: Promising privileged scaffolds for lead discovery within Alzheimer’s disease

Moutayakine, Amina; Marques, C.F.; López, Óscar; Bagetta, Donatella; Leitzbach, Luisa; Hagenow, Stefanie; Carreiro, Elisabete P.; Stark, Holger; Alcaro, Stefano; Fernandez‐Bolanos, J.; Burke, Anthony J.

doi:10.1016/j.bmc.2022.116807

Cited by 7 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The inhibitory activity of 12a–12d against AChE and BuChE was carried out following minor modifications of the Ellman assay, 30 as reported previously 31 using Thermo Scientific TM Varioskan TM LUX microplate reader and Greiner F-bottom 96-well plates.…”

Section: Methodsmentioning

confidence: 99%

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)

Evangelista

López

Puerta

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC 50 = 7–50 µM). For the most potent inhibitor of BuChE, Cornish-Bowden plots were used, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitor demonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheral anionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different as the benzotriazole moiety is accommodated in the catalytic anionic site.

show abstract

Section: Methodsmentioning

confidence: 99%

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)

Evangelista

López

Puerta

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Measuring of the inhibition activity of compounds 9a – 11a and 9b – 11b against cholinesterases (AChE from Electrophorus electricus and BuChE from equine serum) was accomplished following minor modifications of the Ellman assay 35 , as reported previously 36 . A Thermo Scintific TM Varioskan TM LUX microplate reader and Greiner F-bottom 96-well plates were used.…”

Section: Methodsmentioning

confidence: 99%

Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers

Vaaland

López

Puerta

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino- D -arabinitol (DAB) or 1,4-dideoxy-1,4-imino- L -arabinitol (LAB) moiety held together via linkers of variable lengths containing a 1,2,3-triazole ring and 3, 4, or 7 CH 2 groups. The heterodimers were tested as inhibitors of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). The enantiomeric heterodimers with the longest linkers exhibited the highest inhibition potencies for AChE (IC 50 = 9.7 nM and 11 nM) and BuChE (IC 50 = 8.1 nM and 9.1 nM). AChE exhibited the highest enantioselectivity ( ca . 4-fold). The enantiomeric pairs of the heterodimers were found to be inactive (GI 50 > 100 µM), or to have weak antiproliferative properties (GI 50 = 84–97 µM) against a panel of human cancer cells.

show abstract

“…In order to search for novel MAO-B inhibitors, the chromanone structure has been utilized as a promising principal scaffold. − Kong et al reported a series of chromanone derivatives as MAO-B inhibitors, among which compound 5 (Figure ) showed the best MAO-B inhibitory activity (IC 50 = 8.62 nM) . Furthermore, many studies have indicated that both chromanone and synthesized analogues showed good MAO-B inhibitory activities. − Recently, we reported an isochromanone derivative (Figure ) as a potential AChE inhibitor for the treatment of AD …”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer’s Disease

Zhan

et al. 2022

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Based on a multitarget strategy, a series of novel chromanone−1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation demonstrated that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). The optimal compound C10 possessed excellent dual AChE/MAO-B inhibition both in terms of potency and equilibrium (AChE: IC 50 = 0.58 ± 0.05 μM; MAO-B: IC 50 = 0.41 ± 0.04 μM). Further molecular modeling and kinetic investigations revealed that compound C10 was a dual-binding inhibitor bound to both the catalytic anionic site and peripheral anionic site of AChE. In addition, compound C10 exhibited low neurotoxicity and potently inhibited AChE enzymatic activity. Furthermore, compound C10 more effectively protected against mitochondrial dysfunction and oxidation than donepezil, strongly inhibited AChE-induced amyloid aggregation, and moderately reduced glutaraldehyde-induced phosphorylation of tau protein in SH-SY5Y cells. Moreover, compound C10 displayed largely enhanced improvements in cognitive behaviors and spatial memory in a scopolamine-induced AD mice model with better efficacy than donepezil. Overall, the multifunctional profiles of compound C10 suggest that it deserves further investigation as a promising lead for the prospective treatment of AD.

show abstract

Evaluation of chromane derivatives: Promising privileged scaffolds for lead discovery within Alzheimer’s disease

Cited by 7 publications

References 34 publications

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)

Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers

Design, Synthesis, and Biological Evaluation of Novel Chromanone Derivatives as Multifunctional Agents for the Treatment of Alzheimer’s Disease

Contact Info

Product

Resources

About