Нітрозаміщені аурони як інгібітори ксантиноксидази
Aurone derivatives possessing a wide range of biological activities are of high interest in medicinal chemistry. Carboxylated aurones were found previously to inhibit xanthine oxidase, which is a potential target for treatment of hyperuricemia and gout. In this paper, a series of B-ring nitro-substi...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
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| author | Kobzar, Oleksandr L. Mischenko, Iryna M. Tatarchuk, Alona V. Vdovin, Vasyl S. Lukashov, Sergiy S. Yarmoluk, Sergiy M. Vovk, Andriy I. |
| author_facet | Kobzar, Oleksandr L. Mischenko, Iryna M. Tatarchuk, Alona V. Vdovin, Vasyl S. Lukashov, Sergiy S. Yarmoluk, Sergiy M. Vovk, Andriy I. |
| author_institution_txt_mv | [
{
"author": "Oleksandr L. Kobzar",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Iryna M. Mischenko",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Alona V. Tatarchuk",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
},
{
"author": "Vasyl S. Vdovin",
"institution": "Institute of Molecular Biology and Genetics of the NAS of Ukraine, 150 Zabolotnogo St., Kyiv, 03143, Ukraine"
},
{
"author": "Sergiy S. Lukashov",
"institution": "Institute of Molecular Biology and Genetics of the NAS of Ukraine, 150 Zabolotnogo St., Kyiv, 03143, Ukraine"
},
{
"author": "Sergiy M. Yarmoluk",
"institution": "Institute of Molecular Biology and Genetics of the NAS of Ukraine, 150 Zabolotnogo St., Kyiv, 03143, Ukraine"
},
{
"author": "Andriy I. Vovk",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine"
}
] |
| author_sort | Kobzar, Oleksandr L. |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:53Z |
| description | Aurone derivatives possessing a wide range of biological activities are of high interest in medicinal chemistry. Carboxylated aurones were found previously to inhibit xanthine oxidase, which is a potential target for treatment of hyperuricemia and gout. In this paper, a series of B-ring nitro-substituted aurone derivatives were studied in vitro as inhibitors of this enzyme. The introduction of hydroxyl group into the B-ring of nitro-functionalized aurones resulted in significant increase of their inhibitory potency. At the same time, aurones chlorinated at ring A and containing nitro and hydroxyl groups at ring B showed only slightly increased inhibition effect. The kinetic studies and molecular docking calculations were carried out to explain the inhibition mechanism of xanthine oxidase by the nitro-substituted aurone derivatives. |
| doi_str_mv | 10.15407/bioorganica2021.02.012 |
| first_indexed | 2025-07-17T12:19:30Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 2
UDC 547.728.2+577.152.1
DOI: https://doi.org/10.15407/bioorganica2021.02.012
12
Ukrainica Bioorganica Acta
www.bi oorgan ica .org .ua
RESEARCH ARTICLE
Nitro-substituted aurones as xanthine oxidase inhibitors
Oleksandr L. Kobzar1, Iryna M. Mischenko1, Alona V. Tatarchuk1, Vasyl S. Vdovin2,
Sergiy S. Lukashov2, Sergiy M. Yarmoluk2, Andriy I. Vovk1*
1 V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, 1 Murmanska St., Kyiv, 02094, Ukraine
2 Institute of Molecular Biology and Genetics of the NAS of Ukraine, 150 Zabolotnogo St., Kyiv, 03680, Ukraine
Abstract: Aurone derivatives exhibits a wide range of biological activity and are of high interest in medicinal chemistry. Carboxylated
aurones were found previously to inhibit xanthine oxidase, which is a potential target for treatment of hyperuricemia and gout. In this
paper, a series of B-ring nitro-substituted aurone derivatives were studied in vitro as inhibitors of this enzyme. The introduction of
hydroxyl group into the B-ring of nitro-functionalized aurones resulted in significant increase of their inhibitory potency. At the same time,
aurones chlorinated at ring A and containing nitro and hydroxyl groups at ring B showed only a slight increase in inhibition effect. The
kinetic studies and the molecular docking calculations were carried out to explain the inhibition mechanism of xanthine oxidase by the
nitro-substituted aurone derivatives.
Keywords: aurone; xanthine oxidase; inhibition; kinetics; molecular docking.
Introduction
Xanthine oxidase (XO) catalyzes oxidation of
hypoxanthine and xanthine to uric acid at the last stage of
purine catabolism. The reaction proceeds with reduction of
molecular oxygen to superoxide [1, 2]. Excessive activity of
XO in the living cells is accompanied by increasing levels
of uric acid and reactive oxygen species. This may lead to
hyperuricemia, gout, as well as cardiovascular,
inflammatory, and other diseases [3, 4]. One of the
strategies for treatment of hyperuricemia consists in XO in
vivo inhibition [5]. However, adverse effects of allopurinol
and febuxostat manifested in clinical practice [6] make a
reason to search for new compounds active against XO. To
date, many purine and non-purine XO inhibitors of various
chemical structure have been synthesized [7, 8], including
derivatives of imidazole [9], isoxazole [10], thiazole [11],
Received:
Revised:
Accepted:
Published online:
10.08.2021
24.09.2021
12.10.2021
30.12.2021
Corresponding author. Tel.: +380-44-558-5388;
e-mail: vovk@bpci.kiev.ua (A. I. Vovk)
ORCID: 0000-0001-6167-076X
pyrazole [12] and triazole [13]. Natural flavonoids as well
as their synthetic structural analogues [14, 15] such as
chalcone- [16], flavone- [17] and aurone-based compounds
[18, 19] were also studied as XO inhibitors.
Aurones which are important in medicinal chemistry are
considered as beneficial bioactive compounds possessing
antioxidant [20], antiviral [21, 22], antibacterial [23, 24],
anti-inflammatory [25], antimalarial [26] and anticancer
activities [27]. It was previously shown that B-ring
carboxylated aurones inhibit XO with about 50-fold higher
activity in comparison to sulfuretin, a known natural poly-
hydroxylated aurone [18, 19].
Diverse naturally-occurring nitro compounds show a
wide range of bioactivities [28]. For example, nitro flavone
derivative exhibits the cytotoxic activity [29], 4′-nitro-6-
hydroxyflavone suppresses the activity of HNF4α and
stimulates the degradation of HNF4α protein [30],
4-nitro aurone is potential inhibitor of H1N1 virus [31],
5-nitro derivative of protocatechuic aldehyde can be
potential agent for the treatment of gout and hyperuricemia
[32]. Recently, some of the nitro-substituted aurones have
been described as inhibitors of human protein kinase CK2
[33, 34]. In the present study we evaluated the aurone
derivatives having a nitro group in the B-ring as XO
inhibitors.
© Kobzar O. L. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
mailto:vovk@bpci.kiev.ua
https://orcid.org/0000-0001-6167-076X
O. L. Kobzar, I. M. Mischenko, A. V. Tatarchuk et al.
13
Results and Discussion
The most useful method of synthesis of aurones 5 is
condensation of 3-coumaranones 4 with benzaldehydes
[35]. Intermediate 3-coumaranones 4 usually derive from
phenols 1 which can be easily converted into chloroacetic
acid phenyl esters 2 and further with varying success into
ortho-hydroxy-α-halogenoacetophenones 3 in conditions of
Fries rearrangement [36]. Cyclization of intermediates 3
proceeds readily in presence of bases resulting in
3-coumaranones 4 (Scheme 1). Using this method, we have
earlier synthesized aurones 5d-5h unsubstituted in ring A
[32] and derivatives 5i-5k which were halogen-substituted
in ring A [33]. Here we are additionally representing the
synthesis of aurone derivatives having only nitro group in
the various positions of ring B. Condensation of
3-coumaranone with a range of nitro benzaldehydes gave
aurones 5a-5c with high yields. Chemical structures of all
tested compounds are shown in Table 1.
Figure 1. Dose-dependent curves of XO inhibition by compounds
5d (∆), 5e (), and 5k (○).
Nitro-substituted aurone derivatives 5a-5k were studied
in vitro as inhibitors of bovine milk XO characterized by
about 90% amino acid sequence identity to human liver
enzyme [37]. The IC50 values represented in Table 1 were
determined from the dose-dependent curves (Figure 1) as
concentrations of compounds causing 50% inhibition of
enzyme activity. The Hill slope values calculated from the
dose-dependent curves were 1.44±0.33, 1.31±0.19 and
0.99±0.16 for compounds 5d, 5e and 5k, respectively.
These values can be interpreted as possibility of binding a
one molecule of aurone derivative to XO in the inhibition
mechanism.
According to the results obtained (Table 1), the aurone
derivatives 5a-5c bearing nitro group at 4′-, 3′- and
2′-position of B-ring, respectively, did not inhibit XO at
5 µM concentration. However, enzyme inhibition by
compounds 5d and 5e bearing hydroxyl group next to the
nitro group was significantly increased. They showed IC50
values of 0.22 and 0.20 µM, respectively. In contrast, the
shift of hydroxyl group from 3′- or 4′-position of B-ring in
compounds 5d and 5e to 2′-position in compounds 5f and
5g led to a decrease in inhibition of XO that probably is
related to the steric hindrance and consequent twisting of
B-ring to a plane of coumaranone moiety. The IC50 value of
aurone derivative 5h having two hydroxyl groups at the
3′- and 4′-position in addition to the 5′-nitro group is of the
same order of magnitude as the ones of compounds 5d and
5e.
Taking into account these results, the aurone 5e with IC50
value of 0.2 µM was chosen for further optimization. The
introduction of methyl and chlorine substituents into A-ring
(compound 5i) led to decrease of inhibition of XO.
However, chlorinated in A-ring aurone derivatives 5j and
5k showed IC50 values of 0.11 µM and 0.07 µM,
respectively.
Kinetic studies were carried out to elucidate the
mechanism of XO inhibition at four different concentrations
of nitro-substituted aurone derivative 5k and various
concentrations of substrate. According to Lineweaver-Burk
plots presented in Figure 2, the compound is a mixed-type
OH
R
i
O
R
iiO
Cl
OH
R
iii
O
Cl
O
O
iv
O
O
R'
1 2 3
4 5
R R
Scheme 1. Preparation of 3-coumaranones 4 through the Fries rearrangement following synthesis of aurones 5: i) ClCH2COCl, 80-120 ºC,
8 h.; ii) AlCl3, 80-90 °C, 15 min; iii) AcONa ∙ 3H2O, MeOH, 65 °C, 1 h.; iv) R′PhCHO, i-PrOH, HCl, 80 °C 2-8 h.
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 2
14
Table 1. IC50 values for nitro-substituted aurones 5a-k as XO inhibitors.
Compound R4 R5 R6 R7 R2′ R3′ R4′ R5′ IC50, µM
5a H H H H H H NO2 H > 5
5b H H H H H NO2 H H > 5
5c H H H H NO2 H H H > 5
5d H H H H H OH NO2 H 0.22±0.02
5e H H H H H NO2 OH H 0.20±0.04
5f H H H H OH NO2 H H > 5
5g H H H H OH H H NO2 5.06±0.72
5h H H H H H OH OH NO2 0.41±0.06
5i CH3 Cl CH3 H H NO2 OH H 0.43±0.11
5j Cl H H Cl H NO2 OH H 0.11±0.02
5k H Cl H Cl H NO2 OH H 0.07±0.019
inhibitor. A similar inhibition mechanism was reported for
febuxostat [38] and carboxylated aurone derivatives [19].
Calculated values of Ki and Ki′ for nitro-substituted aurone
derivative 5k were 29±0.9 nM and 161±22 nM,
respectively.
Figure 2. Lineweaver-Burk plots for inhibition of XO by
compound 5k. The concentrations of inhibitor were 0 (○) 10 nM
(□), 25 nM (Δ), 75 nM (◊), and 100 nM ().
Molecular docking calculations were performed for
understanding the binding mechanism of nitro-substituted
aurone derivative 5k. The modeling was carried out with
program Autodock Vina [39]. The structure of C chain of
XO was derived from PDB crystal with code 1FIQ [37] and
used for docking calculation. The binding mode of
compound 5k at the active site of XO with docking energy
of -10.4 kcal/mol is presented in Figure 3.
Figure 3. Possible binding mode of compound 5k in the active site
of XO.
In contrast to carboxylated aurone [19], the aurone
scaffold of compound 5k is rotated by 180 º. Nitro group of
the inhibitor has hydrogen bonds with amino acid residues
of Arg880, Thr1010 and water molecule 1457 that interacts
with Glu1261. Hydroxyl group being involved in hydrogen
bond with HOH1457 can also interact with hydroxyl group
of Mo-pterin cofactor, which was represented by water
molecule HOH(MOS1334) in the docking experiments.
Benzylidene fragment of aurone scaffold shows π-stacking
O. L. Kobzar, I. M. Mischenko, A. V. Tatarchuk et al.
15
interaction with Phe914 and may participate in T-shaped
π-stacking interaction with Phe1009. Carbonyl oxygen atom
of benzofuran fragment participates in hydrogen bond
formation with Ser876, while chlorine atoms in position 5
and 7 of A-ring are located near Lys771 and Asn768,
respectively. In addition, the binding mode of the aurone 5k
at the active site of XO includes van der Waals and
electrostatic interactions.
Conclusions
Nitro-substituted aurone derivatives 5a-k were evaluated
in vitro as inhibitors of XO. It was found that introduction
of hydroxyl group into the nitro-functionalized B-ring of
aurone results in over 20-fold increased inhibitory potency
towards the enzyme. The inhibition effects were the same in
case of 3′-hydroxy-4′-nitro- and 4′-hydroxy-3′-nitro-
substituted aurones 5d,e. At the same time, the inhibition by
chlorinated 4′-hydroxy-3′-nitroaurones 5i-k was only
2-3-fold improved. Kinetic studies suggested that nitro-
substituted aurone 5k is a mixed-type inhibitor of XO with
Ki and Ki′ values in the nanomolar and submicromolar
range, respectively. Molecular docking results revealed that
the inhibitor can be accommodated in the enzyme active
site. The obtained data are helpful for further design of
xanthine oxidase inhibitors based on nitro derivatives of
aurone.
Experimental section
Chemistry
Starting materials and solvents were purchased from
commercial suppliers and used without further purification.
Progress of reactions and chromatographic purification of
products was controlled using Merck TLC Silica gel 60 F254
plates in methylene chloride:hexane (70 : 30) solvent
system as an eluent. Structures of synthesized compounds
were confirmed by 1H NMR and 13C NMR spectra that
were recorded on a Varian Mercury 300 instrument at a
302 MHz frequency for 1H NMR spectra and at a 76 MHz
frequency for 13C NMR spectra. Chemical shifts are
described as parts per million (δ) downfield from an internal
standard of tetramethylsilane. All tested compounds have
≥ 95% purity determined by this method.
Synthesis of benzofuran-3(2H)-one (4).
The mixture of 23.5 g (0.25 mol) of phenol 1 and 60 ml
(0.75 mol) of chloroacetyl chloride was refluxed for 8 h in a
1-liter round bottom flask until the total disappearance of
phenol 1 spot on the TLC plate. Then excess chloroacetyl
chloride was evaporated in vacuum. After cooling 50 g
(0.375 mol) of anhydrous aluminum chloride was carefully
added to the oily residue and the flask was heated at 80-
120 °С for a 15 min. Effervescence of the viscous reaction
mixture took place as a result of hydrogen chloride
evolution. After cooling 700 ml of ice water was added to
the resulting melt and the mixture was vigorously stirring
under cooling until total dissolution of the melt. Mixture
was extracted with 2 x 150 ml of dichloromethane.
Combined organic layers were washed with water, filtered
from insoluble precipitate and the solvent was evaporated.
Residue of o-hydroxy-α-chloro-acetophenone 3 was
dissolved in 400 ml of methanol and 102 g (0.75 mol) of
sodium acetate trihydrate was added. Mixture was stirring
and heating under reflux for an 1 h. Then methanol was
evaporated, 300 ml of water was added, and resulting crude
3-coumaranone 4 was extracted with 3 x 100 ml of
dichloromethane. It was finally purified by column
chromatography on silica using dichloromethane : hexane
mixture (70:30, Rf 0.2-0.25). Yield: 8.0 g, 16%; mp 74-
75 °С. 1H NMR (302 MHz, DMSO-d6) δ 7.65 (dt, J 8.7,
1.7 Hz, 1H), 7.59 (dd, J 7.7, 1.6 Hz, 1H), 7.17 (d, J 8.4 Hz,
1H), 7.10 (t, J 7.4 Hz, 1H), 4.67 (d, J 1.6 Hz, 2H).
General procedure of synthesis of aurones 5a-c
0.1 g of coumaranone-3 (4) and 0.113 g of corresponding
nitro-benzaldehyde were dissolved in 3 ml of isopropanol
then 1 drop of hydrochloric acid was added. Reaction
mixture was kept at 80 °С in the water bath during 2-8 h.
Yellow or red-brown precipitate of aurone (5a-c) formed. It
was filtered, carefully washed with ethyl acetate and dried
in the air. When needed, aurone (5a-c) was recrystallized
from 0.5-1 ml of DMF and washed with ethyl acetate.
(2Z)-2-[(4-Nitrophenyl)methylene]benzofuran-3-one
(5a).
Yield: 0.15 g, 75%; Orange crystals; mp 194-196 °C.
1H NMR (302 MHz, DMSO-d6) δ 8.33 (d, J 8.7 Hz, 2H),
8.22 (d, J 8.7 Hz, 2H), 7.84 (t, J 7.7 Hz, 2H), 7.58 (d, J 8.5
Hz, 1H), 7.35 (t, J 7.2 Hz, 1H), 7.07 (s, 1H). 13C NMR
(76 MHz, DMSO-d6) δ 183.7, 165.7, 147.8, 147.2, 138.5,
138.2, 132.0, 124.5, 124.4, 123.9, 120.5, 113.3, 109.1.
(2Z)-2-[(3-Nitrophenyl)methylene]benzofuran-3-one
(5b).
Yield: 0.165 g, 83%; Peach crystals; mp 185-187 °C.
1H NMR (302 MHz, DMSO-d6) δ 8.83 (s, 1H), 8.42 (d,
J 7.7 Hz, 1H), 8.28 (d, J 9.3 Hz, 1H), 7.83 (p, J 8.0 Hz, 3H),
7.61 (d, J 8.2 Hz, 1H), 7.36 (t, J 7.5 Hz, 1H), 7.15 (s, 1H).
13C NMR (76 MHz, DMSO-d6) δ 183.6, 165.6, 148.2,
147.3, 137.0, 133.6, 130.5, 125.2, 124.5, 124.3, 124.1,
120.6, 113.3, 109.5.
(2Z)-2-[(2-Nitrophenyl)methylene]benzofuran-3-one
(5c).
Yield: 0.135 g, 68%; Beige crystals; mp 177-179 °C.
1H NMR (302 MHz, DMSO-d6) δ 8.25 (d, J 7.7 Hz, 1H),
8.16 (d, J 8.3 Hz, 1H), 7.90 (t, J 7.7 Hz, 1H), 7.84 (t, J 8.1
Hz, 2H), 7.71 (t, J 7.7 Hz, 1H), 7.53 (d, J 8.2 Hz, 1H),
7.36 (t, J 7.3 Hz, 1H), 7.18 (s, 1H). 13C NMR (76 MHz,
DMSO-d6) δ 183.5, 165.7, 148.8, 147.5, 138.16, 133.6,
132.2, 130.4, 125.9, 125.0, 124.6, 124.3, 120.5, 113.2,
105.9.
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 2
16
Studies of nitro-substituted aurone derivatives as
inhibitors of xanthine oxidase
Commercially available XO from bovine milk and
xanthine were purchased from firm Sigma-Aldrich. Nitro-
substituted aurone derivatives were studies as inhibitors of
XO in model system contained 0.2 M sodium-phosphate
buffer (pH 7.4), 0.1 mM EDTA, 1% DMSO, inhibitor,
0.008 units/mL of XO, and 50 µM xanthine. After
incubation of the mixture consisted of EDTA, DMSO,
inhibitor, and enzyme during 5 min at 25 °C, the enzymatic
reaction was started by adding xanthine dissolved in
sodium-phosphate buffer. The enzyme activity was
measured spectrophotometrically at 293 nm. Uric acid
molar extinction coefficient of 12.2 mM-1 cm-1 [40] was
used in calculations.
Molecular docking modeling
PDB file 1FIQ [37] was downloaded from Protein Data
Bank server (http://www.rcsb.org) [41]. Docking was
performed into active site of C chain of enzyme. Before
docking simulation, the other chains, cofactor, ligand, and
water molecules were removed from PDB file. The water
molecule named HOH1457, which is involved in the
enzyme catalysis [42] and can participate interaction with
ligand was not removed. Hydroxyl group of Mo-pterin
cofactor was replaced by water molecule named
HOH(MOS1334). The structures of compounds were
drawing in MarvinSketch [43] and optimized by using
MMFF94s force field in program Avogadro [44].
AutoDockTools (version 1.5.6) [45] was used to prepare the
docking files. The molecular docking was performed using
program AutoDock Vina [39]. Analysis of enzyme-inhibitor
complexes was carried out by using Discovery studio
3.5 Visualizer (Accelrys Inc., San Diego, CA, USA).
Notes
The authors declare no conflict of interest.
Author contributions. O. L. K.: conceptualization,
supervision, molecular docking calculation, writing-original
draft. I. M. M.: investigation of bioactivity. A. V. T.:
investigation of bioactivity. V. S. V.: sythesis of
compounds, investigation, formal analysis. S. S. L.: sythesis
of compounds, analysis. S. M. Y.: supervision, writing-
review and editing. A. I. V.: conceptualization, supervision,
writing-review and editing.
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Нітрозаміщені аурони як інгібітори ксантиноксидази
О. Л. Кобзар1, І. М. Міщенко1, А. В. Татарчук1, В. С. Вдовін2, С. С. Лукашов2, С. М. Ярмолюк2, А. І. Вовк2*
1 Інститут біоорганічної хімії та нафтохімії ім. В.П. Кухаря НАН України, вул. Мурманська, 1, Київ, 02094, Україна
2 Інститут молекулярної біології і генетики НАН України, вул. Заболотного, 150, Київ, 03680, Україна
Резюме: Похідні аурону, що виявляють широкий спектр біологічної активності, є перспективними для досліджень у медичній хімії. Раніше було
виявлено, що карбоксильовані аурони інгібують ксантиноксидазу, яка може бути потенційною мішенню для лікування гіперурикемії та подагри.
У представленій роботі in vitro досліджено серію ауронів з нітрогрупою у B-кільці. Введення гідроксильної групи у В-цикл
нітрофункціоналізованих ауронів приводило до значного підвищення їx інгібувального впливу на ксантиноксидазу. У той же час, інгібувальна
дія сполук лише незначно збільшувалася за наявності атомів хлору в А-кільці ауронового каркасу. Для пояснення механізму інгібування
ксантиноксидази нітрозаміщеними ауронами було проведено кінетичні дослідження та розрахунки методом молекулярного докінгу.
Ключові слова: аурони; ксантиноксидаза; інгібування; кінетика; молекулярний докінг.
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| id | oai:ojs2.bioorganica.com.ua:article-21 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:00:33Z |
| publishDate | 2021 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/c8/44d0fed6cd5d1b9c771b1818c285cac8.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-212026-07-19T14:56:53Z Nitro-substituted aurones as xanthine oxidase inhibitors Нітрозаміщені аурони як інгібітори ксантиноксидази Kobzar, Oleksandr L. Mischenko, Iryna M. Tatarchuk, Alona V. Vdovin, Vasyl S. Lukashov, Sergiy S. Yarmoluk, Sergiy M. Vovk, Andriy I. aurone xanthine oxidase inhibition kinetics molecular docking аурони ксантиноксидаза інгібування кінетика молекулярний докінг Aurone derivatives possessing a wide range of biological activities are of high interest in medicinal chemistry. Carboxylated aurones were found previously to inhibit xanthine oxidase, which is a potential target for treatment of hyperuricemia and gout. In this paper, a series of B-ring nitro-substituted aurone derivatives were studied in vitro as inhibitors of this enzyme. The introduction of hydroxyl group into the B-ring of nitro-functionalized aurones resulted in significant increase of their inhibitory potency. At the same time, aurones chlorinated at ring A and containing nitro and hydroxyl groups at ring B showed only slightly increased inhibition effect. The kinetic studies and molecular docking calculations were carried out to explain the inhibition mechanism of xanthine oxidase by the nitro-substituted aurone derivatives. Похідні аурону, що виявляють широкий спектр біологічної активності, є перспективними для досліджень у медичній хімії. Раніше було виявлено, що карбоксильовані аурони інгібують ксантиноксидазу, яка може бути потенційною мішенню для лікування гіперурикемії та подагри. У представленій роботі in vitro досліджено серію ауронів з нітрогрупою у B-кільці. Введення гідроксильної групи у В-цикл нітрофункціоналізованих ауронів приводило до значного підвищення їx інгібувального впливу на ксантиноксидазу. У той же час, інгібувальна дія сполук лише незначно збільшувалася за наявності атомів хлору в А-кільці ауронового каркасу. Для пояснення механізму інгібування ксантиноксидази нітрозаміщеними ауронами було проведено кінетичні дослідження та розрахунки методом молекулярного докінгу. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2021-12-27 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/21 10.15407/bioorganica2021.02.012 Ukrainica Bioorganica Acta; Vol. 16 No. 2 (2021): Ukrainica Bioorganica Acta; 12-17 Ukrainica Bioorganica Acta; Том 16 № 2 (2021): Ukrainica Bioorganica Acta; 12-17 1814-9766 1814-9758 10.15407/bioorganica2021.02 en https://bioorganica.com.ua/index.php/journal/article/view/21/25 Copyright (c) 2021 Oleksandr L. Kobzar, Iryna M. Mischenko, Alona V. Tatarchuk, Vasyl S. Vdovin, Sergiy S. Lukashov, Sergiy M. Yarmoluk, Andriy I. Vovk https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | аурони ксантиноксидаза інгібування кінетика молекулярний докінг Kobzar, Oleksandr L. Mischenko, Iryna M. Tatarchuk, Alona V. Vdovin, Vasyl S. Lukashov, Sergiy S. Yarmoluk, Sergiy M. Vovk, Andriy I. Нітрозаміщені аурони як інгібітори ксантиноксидази |
| title | Нітрозаміщені аурони як інгібітори ксантиноксидази |
| title_alt | Nitro-substituted aurones as xanthine oxidase inhibitors |
| title_full | Нітрозаміщені аурони як інгібітори ксантиноксидази |
| title_fullStr | Нітрозаміщені аурони як інгібітори ксантиноксидази |
| title_full_unstemmed | Нітрозаміщені аурони як інгібітори ксантиноксидази |
| title_short | Нітрозаміщені аурони як інгібітори ксантиноксидази |
| title_sort | нітрозаміщені аурони як інгібітори ксантиноксидази |
| topic | аурони ксантиноксидаза інгібування кінетика молекулярний докінг |
| topic_facet | aurone xanthine oxidase inhibition kinetics molecular docking аурони ксантиноксидаза інгібування кінетика молекулярний докінг |
| url | https://bioorganica.com.ua/index.php/journal/article/view/21 |
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