Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase

Shaik, Jeelan Basha; Yeggoni, Daniel Pushparaju; Kandrakonda, Yelamanda Rao; Penumala, Mohan; Zinka, Raveendra Babu; Kotapati, Kasi Viswanath; Darla, Mark Manidhar; Ampasala, Dinakara Rao; Subramanyam, Rajagopal; Damu, Amooru G.

doi:10.1016/j.bioorg.2019.102960

Cited by 23 publications

(6 citation statements)

References 48 publications

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“…Meanwhile, as the compound level increased, fitted curves had elevated X-intercepts (-1/Km), Y-intercept (1/Vmax) and slopes, which indicated an increase in the Michaelis constant Km, but a decrease in Vmax. Consequently, compound 5 inhibited AChE in a mixed-type competitive manner, and could be an AChE inhibitor with dual binding sites (Shaik et al, 2019;Tang et al, 2019).…”

Section: Kinetic Study On the Inhibitory Effect Of Ache By Compoundmentioning

confidence: 99%

Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Li²,

Wu³

et al. 2023

Front. Plant Sci.

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Plant-derived natural products are important resources for pesticide discovery. Acetylcholinesterase (AChE) is a well-validated pesticide target, and inhibiting AChE proves fatal for insects. Recent studies have shown that the potential of various sesquiterpenoids as AChE inhibitors. However, few studies have been conducted with eudesmane-type sesquiterpenes with AChE inhibitory effects. Therefore, in this research, we isolated two new sesquiterpenes, laggeranines A (1) and B (2), along with six known eudesmane-type sesquiterpenes (3–8) from Laggera pterodonta, and characterized their structures and the inhibitory effect they exerted on AChE. The results showed that these compounds had certain inhibitory effects on AChE in a dose-dependent manner, of which compound 5 had the best inhibitory effect with IC50 of 437.33 ± 8.33 mM. As revealed by the Lineweaver-Burk and Dixon plots, compound 5 was observed to suppress AChE activity reversibly and competitively. Furthermore, all compounds exhibited certain toxicity levels on C. elegans. Meanwhile, these compounds had good ADMET properties. These results are significant for the discovery of new AChE targeting compounds, and also enrich the bioactivity activity repertoire of L. pterodonta.

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Section: Kinetic Study On the Inhibitory Effect Of Ache By Compoundmentioning

confidence: 99%

Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Li²,

Wu³

et al. 2023

Front. Plant Sci.

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“…Cholinesterase inhibitory, antioxidant, neuroprotective, and modulation of A β aggregation activities of flavone-8-acrylamide derivatives were evaluated by Amooru and coworkers. Modest antioxidant activity, strong neuroprotective capacities, accelerated A β aggregation, and selective inhibition of the AChE over BuChE was indicated by these novel multifunctional anti-Alzheimer agents [ 73 ]. Metal ions such as Cu, Fe, and Zn interacted with soluble and aggregated forms of A β peptide leading to the development of AD.…”

Section: Other Synthetic Antioxidant Compounds In Admentioning

confidence: 99%

Antioxidant Compounds in the Treatment of Alzheimer’s Disease: Natural, Hybrid, and Synthetic Products

Hatami

Mortazavi

Baseri

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Alzheimer’s disease (AD) which is associated with cognitive dysfunction and memory lapse has become a health concern. Various targets and pathways have been involved in AD’s progress, such as deficit of acetylcholine (ACh), oxidative stress, inflammation, β-amyloid (Aβ) deposits, and biometal dyshomeostasis. Multiple pieces of evidence indicate that stress oxidative participation in an early stage of AD and the generated ROS could enable neurodegenerative disease leading to neuronal cell death. Hence, antioxidant therapies are applied in treating AD as a beneficial strategy. This review refers to the development and use of antioxidant compounds based on natural products, hybrid designs, and synthetic compounds. The results of using these antioxidant compounds were discussed with the given examples, and future directions for the development of antioxidants were evaluated.

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“…Nowadays, novel and rapid synthetic strategies of flavonoids have been developed and gradually replaced the classical methods. Two-step synthesis from 2-hydroxyacetone and benzoyl chloride has been the most common strategy to generate flavones (Scheme 18a) due to its excellent applicability and convenience [181][182][183]. Firstly, β-propanedione were synthesized from 2-hydroxyacetone and benzoyl chloride via esterification and basemediated Baker-Venkataraman rearrangement.…”

Section: Total-synthesis Strategies Of Flavonoid Derivativesmentioning

confidence: 99%

Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis

Ding

Jiang

Zhang

et al. 2022

Nat. Prod. Bioprospect.

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Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

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Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase

Cited by 23 publications

References 48 publications

Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Acetylcholinesterase inhibitory activity of sesquiterpenoids isolated from Laggera pterodonta

Antioxidant Compounds in the Treatment of Alzheimer’s Disease: Natural, Hybrid, and Synthetic Products

Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis

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