Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2

Weng, Zi-Miao; Ge, Guang-Bo; Dou, Tingfeng; Wang, Ping; Liu, Pingkun; Tian, Xinhui; Qiao, Nan; Yu, Yang; Zou, Li-Wei; Zhou, Qi; Zhang, Weidong; Hou, Jie

doi:10.1016/j.bioorg.2018.01.011

Cited by 59 publications

(33 citation statements)

References 39 publications

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“…Therefore, it is plausible to think that the higher release of this odorant in the wines with HS and phenolic compounds ( Figure 3c) might due to the inhibitory effect of these types of compounds on salivary esterase, reducing the transformation of ethyl hexanoate in the corresponding volatile acid, which might happen in the HS systems without polyphenols. Furthermore, both phenolic extracts seemed to have a high inhibitory activity compared to the monomer catechin and the non-flavonoid compound gallic acid, which is in agreement with the higher inhibitory carboxylesterase capacity of flavonoid-type polyphenols [44]. This funding might also explain previous results [17] in which authors observed a higher decrease in ester release in white wines spiked with human saliva compared to red wines (with flavonoid type polyphenols) when using dynamic headspace conditions.…”

Section: Effect Of Phenolic Compounds On Aroma Volatility In Wines Wisupporting

confidence: 84%

“…However, Figure 3c shows a higher release of this odorant in the systems with polyphenols, and mainly when they were supplemented with phenolic extracts. To explain this, one possible hypothesis can be related to the capacity of certain polyphenols to inhibit some salivary enzymatic activities (α-amylases, carboxylesterases) [41][42][43][44]. It has been demonstrated that human saliva can metabolize carboxylic esters, producing the corresponding carboxylic acids [23,28].…”

Section: Effect Of Phenolic Compounds On Aroma Volatility In Wines Wimentioning

confidence: 99%

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Interactions among Odorants, Phenolic Compounds, and Oral Components and Their Effects on Wine Aroma Volatility

et al. 2020

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To determine the impact of oral physiology on the volatility of typical wine aroma compounds, mixtures of a synthetic wine with oral components (centrifuged human saliva (HS), artificial saliva with mucin (AS), and buccal epithelial cells (BC)) were prepared. Each wine type was independently spiked with four relevant wine odorants (guaiacol, β-phenyl ethanol, ethyl hexanoate, and β-ionone). Additionally, the impact of four types of phenolic compounds (gallic acid, catechin, grape seed extract, and a red wine extract) on aroma volatility in the HS, AS, and BC wines was also assessed. Static headspace was measured at equilibrium by solid phase microextraction–GC/MS analysis. Results showed a significant impact of oral components on the volatility of the four tested odorants. Independently of the type of aroma compound, aroma volatility was in general, higher in wines with BC. Moreover, while guaiacol and ethyl hexanoate volatility was significantly lower in wines with HS compared to wines with AS, β-ionone showed the opposite behavior, which might be related to metabolism and retention of mucin, respectively. Phenolic compounds also showed a different effect on aroma volatility depending on the type of compound and wine. Gallic acid had little effect on polar compounds but it enhanced the volatility of the most hydrophobic ones (ethyl hexanoate and β-ionone). In general, flavonoid type polyphenols significantly reduced the volatility of both polar (guaiacol and β-phenyl ethanol) and hydrophobic compounds (β-ionone in HS and BC wines), but through different mechanisms (e.g., π–π interactions and hydrophobic binding for polar and apolar odorants respectively). On the contrary, flavonoids enhanced the volatility of ethyl hexanoate, which might be due to the inhibition exerted on some salivary enzymes (e.g., carboxyl esterase) involved in the metabolism of this odorant molecule.

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Section: Effect Of Phenolic Compounds On Aroma Volatility In Wines Wisupporting

confidence: 84%

Section: Effect Of Phenolic Compounds On Aroma Volatility In Wines Wimentioning

confidence: 99%

Interactions among Odorants, Phenolic Compounds, and Oral Components and Their Effects on Wine Aroma Volatility

et al. 2020

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“…Molecular docking technology, an algorithm that predicts the putative geometry of a protein-ligand complex has been successfully applied in the studies of SAR of compounds and TCM as well as predicting binding affinities of ligands [18][19][20][21][22]. Irrespective of these gains, there also exist disadvantages such as low accuracy and high false positive rate.…”

Section: Introductionmentioning

confidence: 99%

Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro

Wang

et al. 2020

Molecules

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Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well as investigate their structure activity relationships. Virtual screening using molecular docking technique was used to screen 103 flavonoids. Out of this number, 42 target compounds were selected, and their inhibitory effects on thrombin assayed by chromogenic substrate method. The results indicated that the carbon-carbon double bond group at the C2, C3 sites and the carbonyl group at the C4 sites of flavones were essential for thrombin inhibition, whereas the methoxy and O-glycosyl groups reduced thrombin inhibition. Noteworthy, introduction of OH groups at different positions on flavonoids either decreased or increased anti-thrombin potential. Myricetin exhibited the highest inhibitory potential against thrombin with an IC50 value of 56 μM. Purposively, the established molecular docking virtual screening method is not limited to exploring flavonoid structure activity relationships to anti-thrombin activity but also usefully discovering other natural active constituents.

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“…Furthermore, flavonoids can be easily deteriorated by environmental factors such as temperature, pH, and light. [55][56][57][58] Despite the health benefits, the The predicted affinities of all the investigated molecules signified that flavonones (1-24) were having lower binding affinities compared to flavone derivatives (25)(26)(27)(28)(29)(30)(31)(32)(33). A nonsteroidal flavonoid-based pharmacophore ( Figure 11) was identified as an outcome of molecular docking study that would be an alternative to steroidal scaffold.…”

Section: Resultsmentioning

confidence: 99%

Design and pharmacophoric identification of flavonoid scaffold‐based aromatase inhibitors

Banjare

Verma

Jain

et al. 2020

Journal of Heterocyclic Chem

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Aromatase is a crucial enzyme for the catalysis of aromatization reaction at the last and rate‐limiting step involved in the conversion of androgenic substrates to an estrogenic substrate. A hormone‐dependent breast cancer in postmenopausal woman can be cured by inhibition of estrogen biosynthesis by the help of aromatase inhibitors (AIs). The mode of interactions of flavonones with the active site of aromatase has been studied in search of potent and selective AIs as a substitute of the natural steroidal ligand. Structure‐based computational approach namely, molecular docking simulations were performed to investigate the structural features of the docked complex of aromatase and flavonoid ligands. A nonsteroidal flavonoid pharmacophore showing electrostatic and steric features for selective binding within the main pocket of the catalytic active site of aromatase has been identified as an outcome of the study. The binding affinity of quercetin and isoflavone were predicted within aromatase. Isoflavone was used as a negative control to compare its binding affinities with the selected dataset. The predicted binding affinity of negative control isoflavone was in accordance with its in vitro AI efficacy. Isoflavone showed poor binding affinity and ranked last in terms of MolDock score (−86.309 kcal/molÅ) compared to dataset molecules. The generated pharmacophoric information will be helpful for the synthetic chemist to design and synthesize selective AIs with comparable binding affinity to the natural steroidal ligand.

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Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2

Cited by 59 publications

References 39 publications

Interactions among Odorants, Phenolic Compounds, and Oral Components and Their Effects on Wine Aroma Volatility

Interactions among Odorants, Phenolic Compounds, and Oral Components and Their Effects on Wine Aroma Volatility

Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro

Design and pharmacophoric identification of flavonoid scaffold‐based aromatase inhibitors

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