Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase

Muzychka, Oksana V.; Kobzar, Oleksandr; Попова, Антонина В.; Frasinyuk, M. S.; Vovk, А. I.

doi:10.1016/j.bmc.2017.04.048

Cited by 29 publications

(22 citation statements)

References 41 publications

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“…The synthetic route towards the benzofuropyrazole derivatives was shown in Scheme 1. The 6-methoxybenzofuran-3-(2 H )-one 3 was prepared according to the reported method in three steps [29,30,31] (please refer to the Supplementary Materials). The Hoesch reaction of resorcinol with chloroacetonitrile in the presence of anhydrous ZnCl 2 and HCl gas generated an imine intermediate, which upon hydrolysis, provided 2-chloro-1-(2,4-dihydroxyphenyl)ethanone in 94% yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

et al. 2019

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To find novel antitumor agents, a series of 1H-benzofuro[3,2-c]pyrazole derivatives 4a-e were designed and synthesized. The treatment of 6-methoxybenzofuran-3(2H)-one 3 with LiHMDS in anhydrous tetrahydrofuran (THF) followed by reaction with 3-substitued phenyl isothiocyanate gave the thioamide intermediates, which underwent condensation with hydrazine monohydrate in dioxane/EtOH (1:1) to provide the benzofuropyrazole derivatives 4a–e as well as the unexpected pyrazole derivatives 5a–e. In tumor cell growth inhibitory assay, all the benzofuropyrazole derivatives were not active against the breast tumor MCF-7 cell, only 4a was highly active and more potent than ABT-751 against the leukemia K562 (GI50 = 0.26 μM) and lung tumor A549 cells (GI50 = 0.19 μM), while other benzofuropyrazoles showed very weak inhibitory activity. In contrast, the pyrazoles 5a-e were in general more potent than the benzofuropyrazoles 4a–e. Compound 5a exhibited a similar tendency to that of 4a with high potency against K562 and A549 cells but weak effects on MCF-7 cell. Both pyrazoles 5b and 5e exhibited high inhibitory activities against K562, MCF-7 and A549 cells. The most active compound 5b was much more potent than ABT-751 against K562 and A549 cells with GI50 values of 0.021 and 0.69 μM, respectively. Moreover, 5b was identified as a novel tubulin polymerization inhibitor with an IC50 of 7.30 μM.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

et al. 2019

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“…The assay mixture was then incubated at 25 °C for 10 min. The reaction was terminated by addition of 2 mL of 0.5 N HCl and the absorbance was measured at 295 nm using a spectrophotometer (Thermo Scientific, Waltham, MA) and the molar extinction coefficient of uric acid 12.2 mM −1 cm −1 was used for calculations . The XO kinetic study was carried out using screening of flavonoids (5 to 20 μM) comparing with allopurinol (5 μM) as positive control.…”

Section: Methodsmentioning

confidence: 99%

“…[28] The XO kinetic study was carried out using screening values were expressed as means of three experiments. The type of inhibition was determined using Lineweaver-Burk plots.…”

Section: Ta B L E 2 Antioxidant and Anti-inflammatory Activity Of Flamentioning

confidence: 99%

Antioxidant, anti‐inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives

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et al. 2017

J Biochem & Molecular Tox

107

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The synthesized flavonoid derivatives were examined for their antioxidant, anti-inflammatory, xanthine oxidase (XO), urease inhibitory activity, and cytotoxicity. Except few, all the flavonoids under this study showed significant antioxidant activity (45.6%-85.5%, 32.6%-70.6%, and 24.9%-65.5% inhibition by DPPH, ferric reducing/antioxidant power, and oxygen radical absorption capacity assays) with promising TNF-inhibitory activity (42%-73% at 10 M) and IL-6 inhibitory activity (54%-81% at 10 M) compared with that of control dexamethasone. The flavonoidsO 7 -hexyl chrysin, showed an inhibition with IC 50 values (4.5-8.1 g/mL), more than allopurinol (8.5 g/mL) at 5 M against XO and showing more than 50% inhibition at a final concentration (5 mM) with an IC 50 value of ranging from 4.8 to 7.2 ( g/mL) in comparison with the positive control thiourea (5.8 g/mL) for urease inhibition. Thus, the flavonoid derivatives may be considered as potential antioxidant and antigout agents.

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“…However, the carboxylated aurone derivatives have been shown to be potent XO inhibitors. The carboxylic acid group at the 4′-position of B-ring gave aurones good XO inhibitory activities with IC 50 values lower than sulfuretin but little higher than febuxostat, whereas the A-ring-modified aurones with carboxymethoxy group at the 6-position showed much weaker inhibitory activities (Muzychka, Kobzar, Popova, Frasinyuk, & Vovk, 2017). Minh et al isolated two emodin derivatives from the ethyl acetate extract of the root of Rumex crispus L. The two compounds, chrysophanol and physcion, showed strong inhibition against the activity of XO with IC 50 values of 36.4 and 45.0 μg/mL, respectively (Minh et al, 2019).…”

Section: Aurone and Anthraquinonementioning

confidence: 99%

“…However, the carboxylated aurone derivatives have been shown to be potent XO inhibitors. The carboxylic acid group at the 4′‐position of B‐ring gave aurones good XO inhibitory activities with IC 50 values lower than sulfuretin but little higher than febuxostat, whereas the A‐ring‐modified aurones with carboxymethoxy group at the 6‐position showed much weaker inhibitory activities (Muzychka, Kobzar, Popova, Frasinyuk, & Vovk, 2017). Minh et al.…”

Section: Flavonoidsmentioning

confidence: 99%

Advances in structures required of polyphenols for xanthine oxidase inhibition

et al. 2020

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Polyphenols have been used as natural medicaments for the management of hyperuricemia for a long history. They have been attracted many interests because of the little side effects in curing hyperuricemia, which is an important advantage over the antihyperuricemic drugs. In this review, the structure-activity relationships for polyphenols as xanthine oxidase (XO) inhibitors were discussed. It is concluded that the presence of hydroxyl groups, which influences the inhibitory effects, is closely related to whether the substitutions increase the steric hindrance or disturb the interaction of flavonoid with the catalytic site of XO, and the increased size of the molecule after glycosylation may increase the steric hindrance between flavonoid and XO, and consequently reducing the competitive inhibition behaviors. However, there is no obtained simple general rule that can comprehensively describe the effects of structural alteration on the inhibition activity because the results are varied among different subclasses of polyphenols. In addition, the inhibition mechanisms are mainly assumed as polyphenol binding to the active site of XO and hindering the entrance of xanthine or the discharge of uric acid and diffusion of O 2− radical.

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Carboxylated aurone derivatives as potent inhibitors of xanthine oxidase

Cited by 29 publications

References 41 publications

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

Antioxidant, anti‐inflammatory, and enzyme inhibitory activity of natural plant flavonoids and their synthesized derivatives

Advances in structures required of polyphenols for xanthine oxidase inhibition

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