Analogues of 2′-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase

Sukumaran, Sri Devi; Nasir, Shah Bakhtiar; Tee, Jia Ti; Buckle, Michael J. C.; Othman, Rozana; Rahman, Noorsaadah Abd.; Lee, Vannajan Sanghiran; Bukhari, Syed Nasir Abbas; Chee, Chin Fei

doi:10.1080/14756366.2020.1847100

Cited by 8 publications

(2 citation statements)

References 29 publications

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“…In particular, the indanone moiety of donepezil stacks against Trp279 residue in PAS, while the benzyl ring moiety interacts with Trp 84 residue in CAS [17,18]. Nevertheless, the multifactorial hitting strategy in Alzheimer disease necessitates adapting the multitargeting drug design one [19,20].…”

Section: Introductionmentioning

confidence: 99%

Development of new donepezil analogs: synthesis, biological screening and in silico study rational

et al. 2022

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Fifteen new benzothiophene-based compounds were designed, synthesized, and evaluated as potential anti-Alzheimer agents. Most of the synthesized compounds exhibited remarkable AChE inhibitory activity and effectively inhibited self-mediated β-amyloid protein in vitro. Compound 3g (IC50 = 72.488 ± 3.69 μM) showed a significant β-amyloid inhibitory effect exceeding that of donepezil (IC50 = 87.414 ± 4.46 μM). Furthermore, compound 3j (IC50 = 0.498 ± 0.02 μM) showed the best inhibitory activity comparable to that of donepezil (IC50 = 0.404 ± 0.03 μM). The in vivo evaluation of the promising compounds (3g and 3j) confirmed a significant memory improvement in scopolamine-induced memory impairment model in mice. The molecular docking simulation of compounds 3g and 3j in Torpedo californica-AChE (TcAChE) active site showed a good agreement with the obtained screening results. The in silico ADMET and other physicochemical parameters were also reported.

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Section: Introductionmentioning

confidence: 99%

Development of new donepezil analogs: synthesis, biological screening and in silico study rational

et al. 2022

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“…They are utilised as both biosynthetic precursors of flavonoids and as end products as well 9 . Chalcones have shown different pharmacological activities including acetylcholinestrase inhibition 10 , anti-inflammatory 11 , antimicrobial 12 , antihyperlipidemic 13 , and anticancer activities 14–16 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer

Halim

Hassan

Mohamed

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Novel halogenated phenoxychalcones 2a–f and their corresponding N -acetylpyrazolines 3a–f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC 50 = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC 50 = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38α MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites.

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Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase

Ceyhun

Karaca

Osmaniye

et al. 2021

Archiv der Pharmazie

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According to the cholinergic hypothesis, an increase in the acetylcholine level in Alzheimer's disease patients relatively slows down the symptoms of the disease. The most commonly used drug, donepezil, is a cholinesterase inhibitor. In this study, 12 new chalcones (2a–l) were designed and synthesized. In biological activity studies, the acetylcholinesterase (AChE) and butyrylcholinesterase inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 2d, 2f, 2j, and 2l displayed significant activity against AChE. The compounds 2d, 2f, 2j, and 2l displayed IC50 values of 0.042, 0.024, 0.053, and 0.033 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed significant inhibition of AChE. The inhibitory activities of these compounds for β‐amyloid plaque aggregation were investigated. The enzyme kinetic study was performed to observe the effect of the most active compound 2f on the substrate–enzyme relationship, and a mixed‐type inhibition of AchE was determined. Further, docking simulation also revealed that these compounds (2d, 2f, 2j, and 2l) interacted with the enzyme active site in a similar manner to donepezil. The most active derivative, compound 2f, interacted with the amino acids Trp286, Phe295, Tyr341, Trp86, and Glu202.

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Analogues of 2′-hydroxychalcone with modified C4-substituents as the inhibitors against human acetylcholinesterase

Cited by 8 publications

References 29 publications

Development of new donepezil analogs: synthesis, biological screening and in silico study rational

Development of new donepezil analogs: synthesis, biological screening and in silico study rational

Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer

Design and synthesis of novel chalcone derivatives and evaluation of their inhibitory activities against acetylcholinesterase

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