Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase

Katalinić, Maja; Rusak, Gordana; Barović, Jelena Domaćinović; Šinko, Goran; Jelić, Dubravko; Antolović, Roberto; Kovarik, Zrinka

doi:10.1016/j.ejmech.2009.09.041

Cited by 174 publications

(121 citation statements)

References 19 publications

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“…As A549 line has been widely used as a model system to study human alveolar carcinoma, cytotoxic profile of flavonoids in these cells was previously characterized with the results very similar to those measured in our work. Indeed, the IC 50 value of 72.2 µM for quercetin is close to the inhibitory constants published by Loizzo et al (26), Tan et al (27)(28)(29), Robaszkiewicz et al (30), and Chan et al (31); and IC 50 values more than 100 µM were previously reported for fisetin (32), hesperetin (33-35), luteolin (32,36), chrysin (35), baicalein (34), daidzein (37), and genistein (38). Based on our results presented in this article, cytotoxic activity profiles of flavonoids were rather similar for both A549 and HCC-44 lung cancer lines, despite the gender difference of initial origin of these cells.…”

Section: Discussionsupporting

confidence: 59%

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

et al. 2017

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Abstract. Lung cancer is the malignant disorder associated with a high number of fatalities in women and men worldwide. Despite continuous improvements in diagnostic strategies and therapeutic modalities over the past decades, the prognosis and survival rate of patients suffering from lung cancer are still unsatisfactory and suggest the requirement for further molecular studies with different lung cancer models. In the present study, the anticancer action of two methylated metabolites of quercetin, isorhamnetin and tamarixetin, was assessed by studying their antiproliferative and apoptosis-inducing potential in human lung adenocarcinoma cell lines, A549 and HCC-44. Both methylquercetins decreased the viability of lung cancer cells at doses significantly lower than those effective for parent quercetin. The IC 50 values measured for isorhamnetin were 26.6 and 15.9 µM in A549 and HCC-44 cells, respectively. For tamarixetin, the IC 50 values were 19.6 and 20.3 µM in A549 and HCC-44 cells, respectively. These results were many-fold lower than the respective values for quercetin (72.2 and 107.6 µM for A549 and HCC-44 cells, respectively). Based on the activation of caspase family members, both metabolites induced apoptotic cell death in the tested cell lines, predominantly via the extrinsic pathway in A549 cells and in both intrinsic and extrinsic pathways in HCC-44 cells. As A549 and HCC-44 lines were originally established from a male and female patient, current data may suggst some gender differences in the action of quercetin derivatives. Addition of a methyl group in the 3'-or 4'-position of the B-ring of quercetin significantly increased the anticancer activity of this flavonol towards lung adenocarcinoma cells, which demonstrated that these compounds may be considered as potential novel candidates for the development of future chemotherapeutics in the fight against lung cancer.

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Section: Discussionsupporting

confidence: 59%

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

et al. 2017

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“…Research work has linked the ability of the flavonoids to inhibit BChE potently to the presence or absence of -OH groups on the side phenyl ring of the compounds. 24 The hydroxyl groups of flavonoids form hydrogen bonds with important amino acid residues at the active site of the enzyme. 25 It has been observed that brains of Alzheimer's disease patients show several signs of oxidative stress such as lipid peroxidation, protein oxidation, and damage to mitochondrial and nuclear DNA.…”

Section: Discussionmentioning

confidence: 99%

Antioxidative Properties and Effect of Quercetin and Its Glycosylated Form (Rutin) on Acetylcholinesterase and Butyrylcholinesterase Activities

Ademosun

Oboh

Bello

et al. 2016

J Evid Based Complementary Altern Med

132

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This study sought to investigate the anticholinesterase and antioxidative properties of quercetin and its glycosylated conjugate, rutin. The in vitro inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, inhibition of Fe 2þ -induced lipid peroxidation in rat's brain homogenates, radicals scavenging, and Fe 2þ -chelating abilities of the flavonoids were investigated in vitro with concentrations of the samples ranging from 0.06 to 0.6 mM. Quercetin had significantly higher AChE and BChE inhibitory abilities than rutin. Quercetin also had stronger inhibition of Fe 2þ -induced lipid peroxidation in rat's brain homogenates. Similarly, quercetin had higher radical scavenging abilities than rutin. Quercetin also had stronger Fe 2þ -chelating ability than rutin. The inhibition of cholinesterases and antioxidative properties are possible mechanisms by which the flavonoids can be used in the management of oxidative stress-induced neurodegeneration.

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“…Beside differences in the source (rat brain verses electric eels) and state (homogenates verses purified enzyme) of AChE used, that study employed a much higher concentration of acetylthiocholine substrate (0.5 M) and inhibition was determined at one fixed concentration of inhibitor (20 µM). Katalinic et al (2010) proposed that phenolic compounds are able to interact with amino acid residues defining the active site gorge of AChE via hydrogen bond, hydrophobic and π-π interaction. Multiple hydroxyl groups in the phenolic compound structure were believed to enhance the inhibitory activity because of stronger binding capacity (Fale, Asvensao, Serralheiro, & Haris, 2012).…”

Section: Figure 2 Inhibition Of Electric Eel's Acetylcholine Esterasmentioning

confidence: 99%

Screening Flavonoids for Inhibition of Acetylcholinesterase Identified Baicalein as the Most Potent Inhibitor

Balkis¹,

Tran²,

Lee³

et al. 2015

JAS

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Screening phenolic and polyphenolic compounds for inhibitory activity against electric eels acetylcholinesterase (AChE) identified baicalein, a major flavone derived from the roots of Scutellaria baicalensis, as the most potent inhibitor with IC50 (concentration required for 50% inhibition) of 0.61 µM. None of the hydroxybenzoic and hydroxycinnamic acids screened showed inhibitory activity measured at 100 µM. Structure-activity relationships based on IC50 values of the active flavonoids showed that inhibitory activity (a) required the unsaturated 2-phenyl-chroman structure, (b) has strong requirement for the A-ring A5-OH, A6-OH and A7-OH groups (b) does not depend on B-ring hydroxyl groups, and (d) was reduced by bulky sugar substitution of the saturated C-ring C3-OH. Enzyme kinetic analysis showed that baicalein is a mixed inhibitor of AChE with K 1 (equilibrium constant of dissociation of the inhibitor bound enzyme complex) and K 2 (equilibrium constant of dissociation of the inhibitor bound enzyme-substrate complex) of 0.91 and 1.98 µM, respectively.

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Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase

Cited by 174 publications

References 19 publications

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

Antioxidative Properties and Effect of Quercetin and Its Glycosylated Form (Rutin) on Acetylcholinesterase and Butyrylcholinesterase Activities

Screening Flavonoids for Inhibition of Acetylcholinesterase Identified Baicalein as the Most Potent Inhibitor

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