Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності
In the present work, the synthesis of pyrazoline-thiazolidin-4-one hybrids and their pharmacological properties are described. The structure of compounds is characterized using 1H, 13C NMR, and LC-MS spectra. The antioxidant (DPPH assay), antimicrobial (Gram-positive bacterium Lactobacillus plantaru...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2021
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| author | Holota, Serhii M. |
| author_facet | Holota, Serhii M. |
| author_institution_txt_mv | [
{
"author": "Serhii M. Holota",
"institution": "Danylo Halytsky Lviv National Medical University, 69 Pekarska St., Lviv, 79010, Ukraine; Lesya Ukrainka Volyn National University, 13 Voli Ave., Lutsk, 43025, Ukraine"
}
] |
| author_sort | Holota, Serhii M. |
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| datestamp_date | 2026-07-19T14:56:54Z |
| description | In the present work, the synthesis of pyrazoline-thiazolidin-4-one hybrids and their pharmacological properties are described. The structure of compounds is characterized using 1H, 13C NMR, and LC-MS spectra. The antioxidant (DPPH assay), antimicrobial (Gram-positive bacterium Lactobacillus plantarum, Gram-negative bacterium Escherichia coli, and yeasts Candida albicans, MIC determination), redox (cyclic voltammetry) as well as herbicidal activity (against grass species Agrostis stolonifera) of compounds have been studied. All derivatives have demonstrated radical scavenging activity with IC50 values in the range of 4.67-7.12 mM that were measured by the DPPH test. The tested compounds showed very low antimicrobial and herbicidal activity and no redox peaks were observed in the cyclic voltammetry studies |
| doi_str_mv | 10.15407/bioorganica2021.01.018 |
| first_indexed | 2025-07-17T12:19:45Z |
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 1
UDC 616-093 + 547.789.1
DOI: https://doi.org/10.15407/bioorganica2021.01.018
18
Ukrainica Bioorganica Acta
www.bi oorgan ica .org .ua
RESEARCH ARTICLE
Synthesis of novel pyrazoline-thiazolidin-4-one hybrids and
evaluation of their biological activity
Serhii M. Holota1,2*
1 Danylo Halytsky Lviv National Medical University, 69 Pekarska St., Lviv, 79010, Ukraine
2 Lesya Ukrainka Volyn National University, 13 Voli Ave., Lutsk, 43025, Ukraine
Abstract: In the present work, the synthesis of pyrazoline-thiazolidin-4-one hybrids and their pharmacological properties are described.
The structure of compounds is characterized using 1H, 13C NMR, and LC-MS spectra. The antioxidant (DPPH assay), antimicrobial
(Gram-positive bacterium Lactobacillus plantarum, Gram-negative bacterium Escherichia coli, and yeasts Candida albicans, MIC
determination), redox (cyclic voltammetry) as well as herbicidal activity (against grass species Agrostis stolonifera) of compounds have
been studied. All derivatives have demonstrated radical scavenging activity with IC50 values in the range of 4.67-7.12 mM that were
measured by the DPPH test. The tested compounds showed very low antimicrobial and herbicidal activity and no redox peaks were
observed in the cyclic voltammetry studies.
Keywords: pyrazoline-thiazolidin-4-ones hybrids; DPPH assay; antimicrobial/herbicidal activity; cyclic voltammetry.
Introduction
The last decade has witnessed a growing interest in the
development of redox modulating agents as effective tool in
therapy oxidative-stress associated processes: cancers,
diabetes, inflammatory diseases, neurological disorders, and
others [1-4]. In this context, the structure modified
thiazolidin-4-one and pyrazoline nucleus are prospective
molecular platforms for design antioxidants and redox-
modulating agent design [5-8]. For example, the application
of the mentioned scaffolds is an attractive direction for the
development of selective modulators of Nrf2 and NF-kB
transcription factors, that play a key role in the regulation of
cellular responses to oxidative-stress factors and are
potential drug targets [9-11].
In our early-described researches some types thiazolidin-
4-one hybrids linked through “enamine” linker at C-5 has
Received:
Revised:
Accepted:
Published online:
10.02.2021
25.03.2021
12.04.2021
30.06.2021
Corresponding author. Tel.: +380-97-226-0066;
e-mail: golota_serg@yahoo.com (S. M. Holota)
ORCID: 0000-0002-9892-437X
been synthesized and several compounds been have been
identified with a high level of antibacterial and antifungal
[12-14], anticancer and trypanocidal [15], and anti-
inflammatory activity [16] (Figure 1). In our opinion, the
5-aminomethylidene derivatives have several important
advantages in synthetic variability and structure
optimization processes compared to 5-ylidene analogous.
On the other hand, the pyrazolines possess a wide range
of biological activities and belong to unsaturated
heterocycles that can be oxidized to the corresponding
pyrazoles [17]. These properties are of great interest in the
design and development of potential redox-active
compounds as possible pharmacological agents.
Taking into account the above reasons, the main goal of
the present work was the design and synthesis of novel
“enamine”-bearing pyrazoline-thiazolidin-4-one hybrid mo-
lecules and further evaluation of their antioxidant,
antimicrobial, herbicidal, and redox activities.
Results and Discussion
The synthetic design included two key routes
(Scheme 1). Initially, the derivatives 2a, b were easily
obtained using Holmberg’s protocol (i) [18] from corres-
© Holota S. M. 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.
S. M. Holota
19
Figure 1. The “enamine”-bearing thiazolidin-4-one hybrids as potential pharmacological agents.
ponding aminobenzoic acids 1a, b. The procedure (ii) [15]
was used for synthesis 3a, b from obtained derivatives
2a, b. The convenient synthetic approach [19] starting from
aromatic aldehyde 4a, b, and acetophenone (iii and iv) was
used for the synthesis of diarylpyrazolines 6a, b. The target
pyrazoline-thiazolidin-4-one hybrids 7a-d were synthesized
in satisfactory yields and purity by reacting compounds
3a, b and 6a, b under reflux in ethanol for 30-45 min.
The structures of all synthesized compounds were
confirmed by 1H, 13C NMR spectroscopy, and LC-MS-
spectrometry. Esterification of the carboxylic group of
compounds 3a, b under condition ii was observed by the
appearance of signals from the protons of the ethyl group at
~ 4.31 (q, J = 6.3 Hz) and ~ 1.31 (t, J = 6.3 Hz) ppm in the
1H NMR spectra. In the 1H NMR spectra of derivatives
3a, b and 7a-d the proton signal at C-5 double bond appears
mainly in the field of aromatic protons, and only for
derivative 7b it was observed as a singlet at 7.60 ppm. The
pyrazoline fragment of compounds 7a-d shows the
characteristic patterns of the AMX system for CH2-CH
protons.
The synthesized compounds 7a-d have been evaluated
for their antioxidant activity in vitro in the DPPH
(1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay
[20] in the conditions close to physiological (serial dilutions
of stock methanol solutions at six concentrations of 1.0, 2.0,
4.0, 6.0, 8.0, 10.0 mM + Tris-HCl buffer pH = 7.40,
measurements after 60 min). Ascorbic acid was used as a
reference compound (standard). The IC50 values have been
determined for compounds 7a-d as well as ascorbic acid to
characterize their antioxidant activity (Figure 2).
As a result, the tested compounds 7a-d have low-
moderate activity in DPPH assay, and the established IC50
values of the synthesized compounds were: 4.67 mM (7a),
5.90 mM (7b), 6.05 mM (7c), 7.12 mM (7d), and for
ascorbic acid IC50 = 0.045 mM. It should be noted that this
level of antioxidant activity may be more likely associated
with the presence of phenolic (-OH), and dimethylamino
groups (-N(CH3)2) in compounds 7a-d than with other
molecular fragments. Nevertheless, all tested derivatives
show activity from 8.38 to 13.43 mg/mL that is promising
for searching for new potential antioxidants among this
subtype of hybrid molecules.
Compounds 7a-d were preliminary screened for their
potential antimicrobial activity against Gram-positive
bacteria as Lactobacillus plantarum, Gram-negative
bacteria as Escherichia coli, and yeasts (Candida albicans).
Antimicrobial activity was evaluated in terms of minimum
inhibitory concentrations (MICs), and the values were
compared with standard reference antimicrobial agents
[21-22]. Overall, the tested compounds showed very low
antimicrobial activity against the E. coli and C. albicans
compared to the reference drugs (36.5 µM for ampicillin
and 38.96 µM for fluconazole), Table 1. Only derivative 7c
showed activity with MIC value of 1.25 mM against E. coli,
and derivative 7d showed antifungal activity against
C. albicans with MIC value of 1.25 mM. It is also worth
noting that compounds 7a-d were inactive against
L. plantarum.
The herbicidal activity of the compounds 7a-d was tested
against the monocot grass species Creeping bentgrass
(Agrostis stolonifera). Methanol solutions at the
concentration of 1mg/ml of all compounds were added to
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 1
20
Scheme 1. Synthesis of target pyrazoline-thiazolidin-4-one hybrids 7a-d. Reagents and conditions: i) 1a, b (10 mmole), CS(SCH2COOH)2
(10 mmole), С2H5OH:H2O, reflux, 5h; ii) 2a, b (10 mmole), HC(OС2H5)3 (10 mmole), Ac2O, reflux, 3h; iii) 4a, b (10 mmole),
acetophenone (10 mmole), NaOH (10 mmole); iv) 5a, b (10 mmole), NH2-NH2 (10 mmole), KOH (10 mmole), С2H5OH; v) 3a, b (10
mmole), 6a, b (10 mmole), С2H5OH, reflux, 2h.
0 1 2 3 4 5 6 7 8 9 10 11
0
10
20
30
40
50
60
70
80
90
100
7a, IC50=4.67 mM, R
2
=0.93
7b, IC50=5.90 mM, R
2
=0.92
7c, IC50=6.05 mM, R
2
=0.97
7d, IC50=7.12 mM, R
2
=0.92
Ascorbic acid
IC50=0.045 mM, R
2
=0.99
Concentration (mM)
D
P
P
H
r
a
d
ic
a
ls
i
n
h
ib
it
io
n
(
%
)
Figure 2. The dose-depending DPPH radical inhibition and IC50 values for compounds 7a-d.
the plant seeds and incubated in a minimal medium. Seed
germination was observed after 3 days, and only compound
7b inhibited of grass growth by 15 %. No inhibitory effect
on A. stolonifera was observed in the case of compounds
7a, 7c, and 7d.
The redox activity of 7a-d was evaluated by cyclic
voltammetry technique using stock solutions of compounds
in methanol (C = 5 mM) with the addition of phosphate
buffer solution (pH = 6.40). The glassy carbon working
electrode, a platinum wire counter, and a saturated calomel
electrode were used, and the measurements were performed
at 0 min and after 60 min in the potential range from
-1500 mV to 1500 mV with scan rates between 10 and
100 mV/s. No redox peaks were observed under mentioned
experimental conditions in cyclic voltammetry studies for
tested compounds 7a-d.
S. M. Holota
21
Table 1. Antimicrobial properties of compounds 7a-d (MICs values)
Сompounds/
Microorganisms
E.coli L. plantarum C. albicans
7a 2.5 mM >2.5 mM >2.5 mM
7b >2.5 mM >2.5 mM 2.5 mM
7c 1.25 mM >2.5 mM 2.5 mM
7d 2.5 mM >2.5 mM 1.25 mM
Referencesa,b 36.5 µMa 39.8 µMa 38.96 µMb
- a – ampicillin
- b – fluconazole
Conclusions
In the present paper, a synthesis of the series of new
pyrazoline-thiazolidin-4-one hybrids has been reported. The
structure of the compounds was confirmed using 1H, 13C
NMR, and LC-MS spectra. All synthesized compounds
were evaluated for their antioxidant, antibacterial,
antifungal, herbicidal, and redox properties. The
synthesized hybrid compounds have promising free radical
scavenging activities, and obtained results argue to the next
development of antioxidant agents among these types of
molecules.
Experimental section
General
Commercial reagents were purchased from Merck and
used without purification. Melting points were measured in
open capillary tubes on a BŰCHI B-545 melting point
apparatus and are uncorrected. The elemental analyses (C,
H, N) was performed using the Perkin-Elmer 2400 CHN
analyzer and was within ±0.4% of the theoretical values.
The 1H and 13C NMR spectra were recorded on a Bruker-
500 spectrometer at 500 MHz and 126 MHz using a mixture
of DMSO-d6+CCl4 as a solvent and TMS as an internal
standard. Chemical shift values are reported in ppm units
with use of δ scale. Mass spectra were obtained using
electrospray ionization (ESI) techniques on an Agilent 1100
Series LCMS. The purity of the compounds was checked by
thin-layer chromatography performed with Merck Silica
Gel 60 F254 aluminum sheets. Spots were detected by their
absorption under UV light.
Synthesis
General procedure for the synthesis derivatives 7a-d.
In a round bottom flask is placed by 0.01 mole of 3a or
3b and 6a or 6b, add 10 ml of ethanol. The mixture was
heated at reflux for 2 hours. After cooling, the precipitate
formed is filtered off and recrystallized from DMF-ethanol.
Ethyl (Z)-3-(5-(ethoxymethylene)-4-oxo-2-thioxothiazo-
lidin-3-yl)benzoate (3a)
Yield 52%, mp 163-165 °С. 1H NMR (500 MHz,
DMSO-d6) δ 7.99 (s, 1H), 7.90 (s, 1H), 7.47-7.55 (m, 2H),
4.35 (q, J 6.2 Hz, 2H), 4.15 (q, J 6.3 Hz, 2H), 1.35 (t,
J 6.2 Hz, 3H), 1.15 (t, J 6.3 Hz, 3H). LC/MS m/z 338
(M+H)+. Anal. Calcd. for C15H15NO4S2: C, 53.40;
H, 4.48; N, 4.15. Found: C, 53.50; H, 4.60; N, 4.20.
Ethyl (Z)-4-(5-(ethoxymethylene)-4-oxo-2-thioxothiazo-
lidin-3-yl)benzoate (3b)
Yield 63%, mp 187-189 °С. 1H NMR (500 MHz,
DMSO-d6) 7.90 (s, 1H), 7.84 (d, J 8.6 Hz, 2H), 7.69 (d,
J 8.6 Hz, 2H), 4.35 (q, J 6.2 Hz, 2H), 4.15 (q, J 6.3 Hz, 2H),
1.35 (t, J 6.2 Hz, 3H), 1.15 (t, J 6.3 Hz, 3H). LC/MS m/z
338 (M+H)+. Anal. Calcd. for C15H15NO4S2: C, 53.40;
H, 4.48; N, 4.15. Found: C, 53.60; H, 4.50; N, 4.30.
Ethyl (Z)-3-(5-((5-(2-hydroxyphenyl)-3-phenyl-4,5-
dihydro-1H-pyrazol-1-yl)methylene)-4-oxo-2-thioxothiazo-
lidin-3-yl)benzoate (7a)
Yield 65%, mp 212-214 °С. 1H NMR (500 MHz,
DMSO-d6) δ 9.53 (s, 1H), 8.10-8.00 (m, 2H), 7.99-7.91 (m,
2H), 7.69-7.57 (m, 3H), 7.49-7.39 (m, 3H), 7.28-7.22 (m,
2H), 6.81-6.75 (m, 2H), 5.56 (dd, J 11.3, 7.0 Hz, 1H), 4.31
(q, J 6.3 Hz, 2H), 4.00 (dd, J 18.4, 11.3 Hz, 1H), 3.51 (dd,
J 18.4, 7.0 Hz, 1H), 1.00 (t, J 6.3 Hz, 3H). 13C NMR (126
MHz, DMSO-d6) δ 186.5, 179.3, 167.2, 164.1, 161.4, 159.4,
157.2, 154.0, 151.1, 149.4, 142.2, 139.0, 137.4, 129.7,
128.3, 127.0, 126.2, 121.2, 118.4, 113.9, 92.4, 88.7, 62.5,
13.4. LC/MS m/z 530 (M+H)+. Anal. Calcd. for
C28H23N3O4S2: C, 63.50; H, 4.38; N, 7.93. Found: C, 63.70;
H, 4.50; N, 8.00.
Ethyl (Z)-3-(5-((5-(4-(dimethylamino)phenyl)-3-phenyl-
4,5-dihydro-1H-pyrazol-1-yl)methylene)-4-oxo-2-thioxo-
thiazolidin-3-yl)benzoate (7b)
Yield 67%, mp 228-231 °С. 1H NMR (500 MHz,
DMSO-d6) δ 8.00 (dt, J 7.8, 1.4 Hz, 1H), 7.94-7.89 (m, 2H),
7.78 (t, J 1.9 Hz, 1H), 7.70-7.59 (m, 2H), 7.60 (s, 1H), 7.62-
7.56 (m, 1H), 7.58-7.51 (m, 1H), 7.41 (s, 1H), 7.26-7.21 (m,
2H), 6.79-6.73 (m, 2H), 5.57 (dd, J 11.3, 7.1 Hz, 1H), 4.31
(q, J 6.3 Hz, 2H), 4.00 (dd, J 18.4, 11.3 Hz, 1H), 3.51 (dd, J
ISSN 1814-9758. Ukr. Bioorg. Acta, 2021, Vol. 16, N 1
22
18.5, 7.1 Hz, 1H), 2.90 (s, 6H), 1.31 (t, J 6.3 Hz, 3H).
13C NMR (126 MHz, DMSO-d6) δ 184.4, 179.5, 166.5,
163.6, 160.9, 159.5, 156.8, 154.1, 150.5, 148.5, 141.7,
138.5, 137.1, 129.2, 128.1, 127.3, 125.8, 120.6, 116.3,
112.6, 91.5, 88.7, 64.4, 35.2, 13.1. LC/MS m/z 557
(M+H)+. Anal. Calcd. for C30H28N4O3S2: C, 64.73; H, 5.07;
N, 10.06. Found: C, 64.90; H, 5.20; N, 10.20.
Ethyl (Z)-4-(5-((5-(2-hydroxyphenyl)-3-phenyl-4,5-
dihydro-1H-pyrazol-1-yl)methylene)-4-oxo-2-
thioxothiazolidin-3-yl)benzoate (7c)
Yield 68%, mp 230-232 °С. 1H NMR (500 MHz,
DMSO-d6) 9.50 (s, 1H), 8.11-8.02 (m, 2H), 7.96-7.89 (m,
2H), 7.64-7.53 (m, 3H), 7.48-7.38 (m, 3H), 7.25-7.20 (m,
2H), 6.81-6.74 (m, 2H), 5.56 (dd, J 11.3, 7.0 Hz, 1H), 4.31
(q, J 6.3 Hz, 2H), 4.00 (dd, J 18.4, 11.3 Hz, 1H), 3.51 (dd, J
18.4, 7.0 Hz, 1H), 1.05 (t, J 6.3 Hz, 3H). 13C NMR (126
MHz, DMSO-d6) δ 184.0, 179.1, 166.8, 162.9, 160.7, 159.2,
156.8, 153.3, 150.4, 141.5, 138.3, 137.2, 129.7, 129.4,
128.3, 127.5, 126.9, 113.1, 91.1, 86.5, 64.0, 13.2. LC/MS
m/z 530 (M+H)+. Anal. Calcd. for C28H23N3O4S2: C, 63.50;
H, 4.38; N, 7.93. Found: C, 63.80; H, 4.60; N, 8.10.
Ethyl (Z)-4-(5-((5-(4-(dimethylamino)phenyl)-3-phenyl-
4,5-dihydro-1H-pyrazol-1-yl)methylene)-4-oxo-2-
thioxothiazolidin-3-yl)benzoate (7d)
Yield 71%, mp 244-246 °С. 1H NMR (500 MHz,
DMSO-d6) δ 8.09-8.00 (m, 2H), 7.94-7.88 (m, 2H), 7.65-
7.55 (m, 3H), 7.48-7.38 (m, 3H), 7.26-7.20 (m, 2H), 6.79-
6.72 (m, 2H), 5.56 (dd, J 11.3, 7.0 Hz, 1H), 4.31 (q,
J 6.3 Hz, 2H), 4.00 (dd, J 18.4, 11.3 Hz, 1H), 3.51 (dd,
J 18.4, 7.0 Hz, 1H), 2.90 (s, 6H), 1.05 (t, J 6.3 Hz, 3H).
13C NMR (126 MHz, DMSO-d6) δ 183.7, 178.6, 165.7,
162.7, 160.1, 158.8, 156.2, 153.7, 150.0, 141.3, 138.1,
137.0, 129.9, 129.2, 128.1, 127.3, 126.4, 112.6, 90.8, 86.3,
63.7, 39.0, 13.0. LC/MS m/z 557 (M+H)+. Anal. Calcd. for
C30H28N4O3S2: C, 64.73; H, 5.07; N, 10.06. Found:
C, 65.00; H, 5.10; N, 10.30.
Antioxidant activity (DPPH assay)
DPPH inhibition was determined by using the protocol
[20]. The DPPH radical is stable due to the delocalization of
a spare electron over the molecule, thus preventing dimer
formation. This radical is used in the DPPH radical
scavenging capacity assay to quantify the ability of
antioxidants to quench the DPPH radical. The dark purple
color of DPPH will be lost when it is reduced to its non-
radical form stable organic nitrogen centered free radical
with a dark purple color which when reduced to its non-
radical form by antioxidants becomes colorless. DPPH
radicals are widely used in the model system to investigate
the scavenging activities of several natural compounds.
When the DPPH radical is scavenged, the color of the
reaction mixture changes from purple to yellow with
decreasing of absorbance at wavelength 517 nm. The stock
solutions of compounds were prepared in mixture methanol
+ Tris-HCl buffer pH = 7.40. Then 1 mL of DPPH
(8 mg/100 mL of methanol) solution was added to the
sample and the blank. This setup was left at room
temperature for 30 min (vortexed in between). Absorbance
was taken at 517 nm against the ethanol by using UV-1800
spectrophotometer (Shimadzu, Japan). Each sample was
analyzed in triplicate. The percentage of inhibition was
calculated against blank:
I% = (Ablank - (Asample + dpph - Asample))/Ablank × 100%,
where Ablank – is the absorbance of the control reaction
(containing all reagents except the tested compounds);
Asample+dpph – is the absorbance of the tested compounds
after 60 min incubation with DPPH solution;
Asample – is the absorbance of the tested compounds without
DPPH solution.
Antimicrobial activity
The minimal inhibitory concentrations (MICs) were
determined by the standard microdilution method in cation-
adjusted Mueller-Hinton II Broth (MHB, Becton-
Dickinson, Germany) according to the recommendations of
the Clinical and Laboratory Standard Institute. The tested
compounds were evaluated for their antimicrobial activity
against Gram-positive bacteria (L. plantarum), Gram-
negative bacteria (E. coli), and yeasts (C. albicans).
Ampicillin was used as a reference antibacterial agent and
fluconazole as antifungal one. A representative colony was
lifted off with a wire loop and placed in 5 mL of nutrient
broth medium, which was then incubated with shaking at
37 °C for 5 h. Then, 1×106 cells/mL were suspended in a
nutrient broth medium to generate the working suspension.
Different concentrations of peptides were prepared in a
96-well plate using nutrient broth medium, and each well
contained 100 µL compound solutions. A 100-µL cell
working suspension was then added to each well. The plate
was incubated at 37 °C for 24 h, and the optical density
(OD) of each well was then measured at 600 nm after
gently shaking the plate for 10s using a Hybrid Multi-Mode
Microplate reader (BioTek, Synergy H4). Wells containing
medium only (blank) and wells containing cells in medium
without peptides (positive control) were included on the
same plate. The values of MIC were recorded after 20 h and
24 h of incubation with the compounds for bacteria and
yeasts, respectively. Experiments were performed in
triplicate and on three different occasions (i.e., a total of
nine repeats for each individual measurement).
Herbicidal activity - Herbicidal Pre-emergence Test
Seeds of A. stolonifera (JuliwaHESA, Heidelberg,
Germany) were placed into the wells of a 96-well microtiter
plate (Sarstedt, Nümbrecht, Germany). A solution
containing 2.2 g/l Murashige & Skoog plant salts (Serva,
Heidelberg, Germany) and 1.6 g/l Gamborg’s B5 plant
medium (Serva, Heidelberg, Germany) was added to the
wells. The stock solutions in concentration 1 mg/ml in
methanol were prepared for compounds 7a-d and were
added to the wells. Identical volumes of methanol without
compounds were used as a toxicity test of the organic
solvent. The solution containing the plant medium was used
as a negative control. The plate was closed and incubated at
S. M. Holota
23
room temperature under constant light (Osram Fluora lamp)
in a humidity chamber. After 3 days of incubation, the plate
lid was removed and a container with tap water was placed
inside the chamber for increasing the air humidity. The
plate was incubated up to 6 days. Three technical replicates
were performed.
Voltammetric parameters and electrochemical cells
Voltammetric experiments were performed using BAS
100W Potentiostat.A glassy carbon (GC) (A = 0.07 cm2)
was used as working electrode. Pt wire and saturated
calomel electrode (SCE) were used as counter and reference
electrodes. Before each experiment, the surface of GCE was
polished with diamond spray (particle size 1 µm) followed
by thorough rinsing with distilled water. All the
voltammetric experiments were conducted in a high purity
nitrogen atmosphere at room temperature (25 ± 1 °C)
potential range from -1500 mV to 1500 mV, scan rates
between 10 and 100 mV/s; stock solutions in methanol
C = 5 mM, PBS pH = 6.40; measurements at 0 and after
60 min. For reproducible experimental results, the polished
working electrode was used to place in the desired
electrolyte solution followed by recording of various
voltammograms until the achievement of steady state
baseline.
Notes
Acknowledgments and finances. This work was partially
supported by COST Action NutRedOx-CA16112
“Personalized Nutrition in ageing society: redox control of
major age-related diseases”. The author is grateful to
A. Luzhetskyy, A. Palusczak and M. Stierhof (Department
of Pharmaceutical Biotechnology, Saarland University,
Germany), for support with LC-MS, NMR spectra, and
herbicidal activity study.
The author declare no conflict of interest.
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24
Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та
оцінка їх біологічної активності
C. M. Голота1,2*
1 Львівський національний медичний університет імені Данила Галицького, вул. Пекарська, 69, Львів, 79010, Україна
2 Волинський національний університет імені Лесі Українки, просп. Волі, 13, Луцьк, 43025, Україна
Резюме: Протягом останніх десятиріч гібридні молекули на основі піразолінових та тіазолідин-4-онових каркасів є об’єктом інтенсивних
досліджень в медичній хімії як джерело потенційних біологічно активних сполук із широким фармакологічним профілем. В даній роботі
запропонований та представлений ефективний підхід до синтезу піразолін-тіазолідин-4-онових гібридних молекул з єнаміновим лінкером у
молекулах. Структура синтезованих сполук підтверджена з використанням методів 1H-, 13C-ЯМР спектроскопії та РХ-МС-спектрометрії. Для всіх
сполук досліджена антиоксидантна (DPPH метод), протимікробна (по відношенню до грам-позитивних Lactobacillus plantarum, грам-негативних
Escherichia coli та грибів Candida albicans, визначення МІК), редокс (метод циклічної вольтметрії) та гербіцидна активності (по відношенню до
Agrostis stolonifera). Всі тестовані сполуки продемонстрували здатність інгібувати радикали в умовах DPPH-тесту з IC50 в межах 4.67-7.12 mM.
Отримані результати скринінгу антирадикальної активності є аргументом для поглиблених досліджень із застосуванням
додаткових/альтернативних експериментальних моделей, а також оптимізації молекулярної структури. Всі тестовані сполуки проявили низьку
протимікробну та гербіцидну активності, а також не володіють редокс-властивостями.
Ключові слова: піразолін-тіазолідин-4-онові гібриди; метод DPPH; протимікробна/гербіцидна активність; циклічна вольтметрія.
Antioxidant activity (DPPH assay)
Antimicrobial activity
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| id | oai:ojs2.bioorganica.com.ua:article-44 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:01:01Z |
| 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/47/6b97ce15fae74420e70d9ec716e25847.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-442026-07-19T14:56:54Z Synthesis of novel pyrazoline-thiazolidin-4-one hybrids and evaluation of their biological activity Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності Holota, Serhii M. pyrazoline-thiazolidin-4-ones hybrids DPPH assay antimicrobial/herbicidal activity cyclic voltammetry піразолін-тіазолідин-4-онові гібриди метод DPPH протимікробна/гербіцидна активність циклічна вольтметрія In the present work, the synthesis of pyrazoline-thiazolidin-4-one hybrids and their pharmacological properties are described. The structure of compounds is characterized using 1H, 13C NMR, and LC-MS spectra. The antioxidant (DPPH assay), antimicrobial (Gram-positive bacterium Lactobacillus plantarum, Gram-negative bacterium Escherichia coli, and yeasts Candida albicans, MIC determination), redox (cyclic voltammetry) as well as herbicidal activity (against grass species Agrostis stolonifera) of compounds have been studied. All derivatives have demonstrated radical scavenging activity with IC50 values in the range of 4.67-7.12 mM that were measured by the DPPH test. The tested compounds showed very low antimicrobial and herbicidal activity and no redox peaks were observed in the cyclic voltammetry studies Протягом останніх десятиріч гібридні молекули на основі піразолінових та тіазолідин-4-онових каркасів є об’єктом інтенсивних досліджень в медичній хімії як джерело потенційних біологічно активних сполук із широким фармакологічним профілем. В даній роботі запропонований та представлений ефективний підхід до синтезу піразолін-тіазолідин-4-онових гібридних молекул з єнаміновим лінкером у молекулах. Структура синтезованих сполук підтверджена з використанням методів 1H-, 13C-ЯМР спектроскопії та РХ-МС-спектрометрії. Для всіх сполук досліджена антиоксидантна (DPPH метод), протимікробна (по відношенню до грам-позитивних Lactobacillus plantarum, грам-негативних Escherichia coli та грибів Candida albicans, визначення МІК), редокс (метод циклічної вольтметрії) та гербіцидна активності (по відношенню до Agrostis stolonifera). Всі тестовані сполуки продемонстрували здатність інгібувати радикали в умовах DPPH-тесту з IC50 в межах 4.67-7.12 mM. Отримані результати скринінгу антирадикальної активності є аргументом для поглиблених досліджень із застосуванням додаткових/альтернативних експериментальних моделей, а також оптимізації молекулярної структури. Всі тестовані сполуки проявили низьку протимікробну та гербіцидну активності, а також не володіють редокс-властивостями V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2021-06-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/44 10.15407/bioorganica2021.01.018 Ukrainica Bioorganica Acta; Vol. 16 No. 1 (2021): Ukrainica Bioorganica Acta; 18-24 Ukrainica Bioorganica Acta; Том 16 № 1 (2021): Ukrainica Bioorganica Acta; 18-24 1814-9766 1814-9758 10.15407/bioorganica2021.01 en https://bioorganica.com.ua/index.php/journal/article/view/44/44 Copyright (c) 2021 Serhii M. Holota https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | піразолін-тіазолідин-4-онові гібриди метод DPPH протимікробна/гербіцидна активність циклічна вольтметрія Holota, Serhii M. Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| title | Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| title_alt | Synthesis of novel pyrazoline-thiazolidin-4-one hybrids and evaluation of their biological activity |
| title_full | Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| title_fullStr | Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| title_full_unstemmed | Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| title_short | Синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| title_sort | синтез нових піразолін-тіазолідин-4-онових гібридних молекул та оцінка їх біологічної активності |
| topic | піразолін-тіазолідин-4-онові гібриди метод DPPH протимікробна/гербіцидна активність циклічна вольтметрія |
| topic_facet | pyrazoline-thiazolidin-4-ones hybrids DPPH assay antimicrobial/herbicidal activity cyclic voltammetry піразолін-тіазолідин-4-онові гібриди метод DPPH протимікробна/гербіцидна активність циклічна вольтметрія |
| url | https://bioorganica.com.ua/index.php/journal/article/view/44 |
| work_keys_str_mv | AT holotaserhiim synthesisofnovelpyrazolinethiazolidin4onehybridsandevaluationoftheirbiologicalactivity AT holotaserhiim sinteznovihpírazolíntíazolídin4onovihgíbridnihmolekultaocínkaíhbíologíčnoíaktivností |