Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

Tran, Thai-Son; Tran, Thanh-Dao; Tran, The-Huan; Nguyen, Ngoc-Le; Thai, Khac-Minh

doi:10.3390/molecules25184064

Cited by 20 publications

(25 citation statements)

References 51 publications

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“…For instance, Lee et al analyzed several phlorotannins that interacted also with some of the residues above referred, especially eckol (Figure 7) [53]. Kashyap et al observed that two plant natural compounds, reserpine and ajmalicine (Figure 7), also interacted with some of the most rele- Similar to what occurs for synthetic compounds, flavone derivatives (PDB#6EQM), specifically baicalein and diosmetin derivatives [57], 2-phenylbenzimidazoles (PDB#1FKN) [58], 7,8-dihydroxyflavone derivatives (PDB#2ZHS) [59], molecular hybrids of 2-pyridylpiperazine and 5-phenyl-1,3,4-oxadiazoles (PDB#2ZJM), especially compound 4 [60], and quinazolinonebased hydrazones (PDB#4B70) [61], also have demonstrated very promising in silico results that can result in novel drug candidates for BACE-1 inhibition, as shown in (Figure 8). Tran et al [62] built a 2D-QSAR model (R 2 of 0.83) based on the structure of BACE-1 inhibitors found in the literature to identify novel potential inhibitors in a library of chalcone derivatives.…”

Section: β-Secretasementioning

confidence: 80%

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

et al. 2021

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Neurodegenerative diseases (ND), including Alzheimer’s (AD) and Parkinson’s Disease (PD), are becoming increasingly more common and are recognized as a social problem in modern societies. These disorders are characterized by a progressive neurodegeneration and are considered one of the main causes of disability and mortality worldwide. Currently, there is no existing cure for AD nor PD and the clinically used drugs aim only at symptomatic relief, and are not capable of stopping neurodegeneration. Over the last years, several drug candidates reached clinical trials phases, but they were suspended, mainly because of the unsatisfactory pharmacological benefits. Recently, the number of compounds developed using in silico approaches has been increasing at a promising rate, mainly evaluating the affinity for several macromolecular targets and applying filters to exclude compounds with potentially unfavorable pharmacokinetics. Thus, in this review, an overview of the current therapeutics in use for these two ND, the main targets in drug development, and the primary studies published in the last five years that used in silico approaches to design novel drug candidates for AD and PD treatment will be presented. In addition, future perspectives for the treatment of these ND will also be briefly discussed.

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Section: β-Secretasementioning

confidence: 80%

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

et al. 2021

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“…All chemicals were obtained from commercial suppliers and used without further purification. Melting points determination, UV (ultraviolet), IR (infrared), HR-MS (high-resolution mass spectrometry), 1 H-NMR (proton nuclear magnetic resonance), and 13 C-NMR (carbon-13 nuclear magnetic resonance) spectra elucidation and all computation processes were performed on the systems as described earlier [16].…”

Section: Methodsmentioning

confidence: 99%

“…Assay. AChE inhibitory activity was determined using the materials and methods as described earlier [16]. e initial mixture in each well consisted of phosphate buffer pH 8, sample (studied compounds or reference) prepared at different concentrations in dimethyl sulfoxide, and AChE enzyme solution 0.25 UI/mL (in phosphate buffer).…”

Section: Acetylcholinesterase Inhibitionmentioning

confidence: 99%

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Synthesis and Evaluation of the Acetylcholinesterase Inhibitory Activities of Some Flavonoids Derived from Naringenin

Tran

et al. 2021

The Scientific World Journal

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Alzheimer’s disease (AD) is an irreversible neurodegenerative disease that affects many older people adversely. AD has been putting a huge socioeconomic burden on the healthcare systems of many developed countries with aging populations. The need for new therapies that can halt or reverse the progression of the disease is now extremely great. A research approach in the finding new treatment for AD that has attracted much interest from scientists for a long time is the reestablishment of cholinergic transmission through inhibition of acetylcholinesterase (AChE). Naringenin is a flavonoid with the potential inhibitory activity against AChE. From naringenin, many other flavonoid derivatives, such as flavanones and chalcones, can be synthesized. In this study, by applying the Williamson method, nine flavonoid derivatives were synthesized, including four flavanones and five chalcones. The evaluation of AChE inhibitory activity by the Ellman method showed that there were four substances (2, 4, 5, and 7) with relatively good biological activities (IC50 < 100 μM), and these biological activities were better than that of naringenin. The molecular docking revealed that strong interactions with amino acid residue Ser200 of the catalytic triad and those of the peripheral region of the enzyme were crucial for strong effects against AChE. Compound 7 had the strongest AChE inhibitory activity (IC50 13.0 ± 1.9 μM). This substance could be used for further studies.

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“…Evidences from available literatures confirmed existing drugs against the receptors identified. Pepstatin inhibits Cathepsin-D (Knight and Barrett 1976;Fox et al 2016), belnacasan and z-yad-fmk are inhibitors of Caspase-1 (MacKenzie et al 2010;Chopra et al 2009), crytotanshinone, niclosamide and napabucasin inhibit STAT3 (Li et al , 2013(Li et al , 2020, Phenserine inhibits BACE2 (Chang et al 2017), BACE1 inhibited by elenbecestat and umibecestat (Adewole and Ishola 2021;Tran et al 2020), aliskiren strongly binds and inhibits Renin (Wal et al 2011), SRC inhibited by kx-2391, bosutinib and saracatinib (Naing et al 2013, Vultur et al 2008Gucalp et al 2011), ulixertinib and ravoxertinib inhibit MAPK1 (Braicu et al 2019), enalapril, benazepril inhibit ACE (Jackson et al 1984;Yu et al 2006), hydroxychloroquine inhibits ACE2 (Fu et al 2021), HMG-CoA, rosuvastatin and simavastatin targeted against HMG-CoA (Abletshauser et al 2002;Slater and MacDonald 1988) and hydroxyurea inhibits RDR (Keikhaei et al 2016;Singh and Xu 2016).…”

Section: Existing Drug Candidates Against the Human Receptorsmentioning

confidence: 99%

In silico design of bioactive chimeric peptide from archaeal antimicrobial peptides

Banerjee

Chakraborty

Majumder

2021

Preprint

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The adverse role of multi-drug resistant bacterial biofilms accelerating human chronic diseases has posed a great risk to present world. Devising a therapy to impede such perilous effects is the need of the moment. So, in this study, we have designed a novel peptide therapy involving archaeal antimicrobial peptides. In silico predictions assign the peptide construct to be antigenic, non-allergenic, anti-cancerous and having stable physicochemical properties. Computational tools predict intracellular receptors in Escherichia coli and human to be possible binding targets of the construct. In silico docking of modelled peptide with targets, validated the predicted estimations. Coincidentally few human receptors binding strongly to the peptide, tend to be the widely recognized targets associated to human diseases with severe complications. Studies of conformational dynamics of peptide docked complexes with human and bacterial targets, indicated stable binding of the modelled construct. Certainly, the designed peptide could be a potent therapeutic against biofilms and human disorders.

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Synthesis, In Silico and In Vitro Evaluation of Some Flavone Derivatives for Acetylcholinesterase and BACE-1 Inhibitory Activity

Cited by 20 publications

References 51 publications

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

Recent Developments in New Therapeutic Agents against Alzheimer and Parkinson Diseases: In-Silico Approaches

Synthesis and Evaluation of the Acetylcholinesterase Inhibitory Activities of Some Flavonoids Derived from Naringenin

In silico design of bioactive chimeric peptide from archaeal antimicrobial peptides

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