Synthesis and biological evaluation of coumarin derivatives containing oxime ester as α-glucosidase inhibitors

Zhang, Xin; Zheng, Yingying; Hu, Chunmei; Wu, Xiao-Zheng; Lin, Jing; Xiong, Zhuang; Zhang, Kun; Xu, Xuetao

doi:10.1016/j.arabjc.2022.104072

Cited by 56 publications

(18 citation statements)

References 30 publications

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“…2(C,D), all the segments/replots were linear but with different slopes and intercepts, and intersected in the second quadrant, indicating that both EGC and EGCG were hybrid inhibitors capable of binding directly to free ⊍-glucosidase and the enzyme-substrate complex. 34 The terminal site of ⊍-glucosidase substrates typically exhibits three adjacent hydroxyl groups on the same sixmembered ring, which serve as the active site for ⊍-glucosidase.…”

Section: Inhibition Kinetics On ⊍-Glucosidasementioning

confidence: 99%

Molecular insights into α‐glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (−)‐epigallocatechin‐3‐gallate

et al. 2023

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BACKGROUNDDiabetes mellitus poses a substantial threat to public health due to rising morbidity and mortality. α‐Glucosidase is one of the key enzymes affecting diabetes. Herein, (−)‐epigallocatechin‐3‐gallate (EGCG) and (−)‐epigallocatechin (EGC) were applied to clarify the role of the galloyl moiety of tea polyphenols in the inhibition of glycation and α‐glucosidase activity. The structure–activity relationship of the galloyl moiety in EGCG on α‐glucosidase was investigated in terms of inhibition kinetics, spectroscopy, atomic force microscopy and molecular docking. A bovine serum protein–fructose model was employed to determine the effect of the galloyl moiety on glycation.RESULTSThe results indicated that the introduction of a galloyl moiety enhanced the capacity of EGCG to inhibit glycation and α‐glucosidase activity. The IC50 value of EGC is approximately 2400 times higher than that of EGCG. Furthermore, the galloyl moiety in EGCG altered the microenvironment and secondary structure of α‐glucosidase, resulting in a high binding affinity of EGCG to α‐glucosidase. The binding constant of EGCG to α‐glucosidase at 298 K is approximately 28 times higher than that of EGC.CONCLUSIONOverall, the galloyl moiety of EGCG plays a crucial role in inhibiting glycation and α‐glucosidase activity, which helps to enhance the molecular understanding of the structure and function of the polyphenol galloyl moiety in the science of food and agriculture. © 2023 Society of Chemical Industry.

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Section: Inhibition Kinetics On ⊍-Glucosidasementioning

confidence: 99%

Molecular insights into α‐glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (−)‐epigallocatechin‐3‐gallate

et al. 2023

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“…The α-glucosidase inhibitory activity of compounds ( 1 ∼ 6 ) was detected as described in previous reports ( Adisakwattana et al, 2009 ; Adisakwattana et al, 2013 ; Zhang et al, 2022 ). 10 μl α-glucosidase solution, 10 μl compound were added into 80 μl phosphate buffer, and the mixture was incubated for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of activity evaluation of flavonoid derivatives as ɑ-glucosidase inhibitors

Zhu

Zhong

2022

Front. Chem.

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Six flavonoid derivatives were synthesized and tested for anti-α-glucosidase activities. All derivatives were confirmed using NMR and HRMS and exhibited excellent inhibitory effects on α-glucosidase. Derivative four exhibited the highest anti-α-glucosidase activity (IC50: 15.71 ± 0.21 μM). Structure-activity relationship results showed that bromine group would be the most beneficial group to anti-α-glucosidase activity. Inhibitory mechnism and inhibition kinetics results showed derivative four was a reversible and mixed-type inhibitor. Molecular docking revealed that derivative four was tightly bind to the amino acid residues of active pocket of α-glucosidase and formed hydrogen bond, π-π stacking, and Pi-Donor hydrogen with α-glucosidase. Moreover, the physicochemical parameters of all derivatives were assessed using SwissADME software. This results also showed that the hybridization of flavonoid and phenylpropionic acid would be a useful strategy for the development of α-glucosidase inhibitors.

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“…Multiple BRD4 protein small-molecule inhibitors, such as JQ1, have been developed and have shown promising anticancer results in experimental and clinical cancer studies ( White et al, 2019 ). However, limitations of these BRD4 inhibitors were also displayed ( Zhang et al, 2022 ). Some studies have shown that the accumulation of BRD4 protein is a key factor which confers resistance to BET inhibitors ( Janouskova et al, 2017 ; Jin et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Lethal activity of BRD4 PROTAC degrader QCA570 against bladder cancer cells

Wang

Zhang

et al. 2023

Front. Chem.

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Bladder cancer is the most common malignancy of the urinary system. Efforts to identify innovative and effective therapies for bladder cancer are urgently needed. Recent studies have identified the BRD4 protein as the critical factor in regulation of cell proliferation and apoptosis in bladder cancer, and it shows promising potential for pharmacologic treatment against bladder cancer. In this study, we have evaluated the biological function of QCA570, a novel BET degrader, on multiple bladder cancer cells and explore its underlying mechanisms. QCA570 potently induces degradation of BRD4 protein at nanomolar concentrations, with a DC50 of ∼ 1 nM. It decreases EZH2 and c-MYC levels by transcriptional suppression and protein degradation. Moreover, the degrader significantly induces cell apoptosis and cycle arrest and shows antiproliferation activity against bladder cancer cells. These findings support the potential efficacy of QCA570 on bladder cancer.

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Synthesis and biological evaluation of coumarin derivatives containing oxime ester as α-glucosidase inhibitors

Cited by 56 publications

References 30 publications

Molecular insights into α‐glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (−)‐epigallocatechin‐3‐gallate

Molecular insights into α‐glucosidase inhibition and antiglycation properties affected by the galloyl moiety in (−)‐epigallocatechin‐3‐gallate

Synthesis of activity evaluation of flavonoid derivatives as ɑ-glucosidase inhibitors

Lethal activity of BRD4 PROTAC degrader QCA570 against bladder cancer cells

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