Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону
Eleven spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives were synthesized, and their antifungal activity against Candida albicans and Cryptococcus neoformans was tested. Among synthesized derivatives, one antifungal-active substance was revealed – 6-fluorospiro[chromane-2,3ʹ-pyrrolidine]-4-one hydr...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
2025
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|---|---|
| author | Sapelkin, Vladislav M. Lukashov, Sergiy S. Bieda, Oleksandr A. Yarmoluk, Sergiy M. |
| author_facet | Sapelkin, Vladislav M. Lukashov, Sergiy S. Bieda, Oleksandr A. Yarmoluk, Sergiy M. |
| author_institution_txt_mv | [
{
"author": "Vladislav M. Sapelkin",
"institution": "Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine "
},
{
"author": "Sergiy S. Lukashov",
"institution": "Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine "
},
{
"author": "Oleksandr A. Bieda",
"institution": "Scientific Service Company «OTAVA», LLC, Kyiv, Ukraine"
},
{
"author": "Sergiy M. Yarmoluk",
"institution": "Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine "
}
] |
| author_sort | Sapelkin, Vladislav M. |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:55Z |
| description | Eleven spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives were synthesized, and their antifungal activity against Candida albicans and Cryptococcus neoformans was tested. Among synthesized derivatives, one antifungal-active substance was revealed – 6-fluorospiro[chromane-2,3ʹ-pyrrolidine]-4-one hydrochloride inhibiting growth of Cryptococcus neoformans with the MIC value 16 μg/ml. This compound demonstrates no cytotoxicity or hemolytic activity against human cell line HEK-293 and red blood cells. |
| doi_str_mv | 10.15407/bioorganica2025.01.050 |
| first_indexed | 2025-07-17T12:20:07Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2025, Vol. 20, N 1
UDC 547.814 + 547.741
DOI: https://doi.org/10.15407/bioorganica2025.01.050
50
Ukrainica Bioorganica Acta
www.bi oorgan ica .org .ua
SHORT COMMUNICATION
Synthesis of some spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives and
investigation of their antifungal activity
Vladislav M. Sapelkin1, Sergiy S. Lukashov1, Oleksandr A. Bieda2, Sergiy M. Yarmoluk1
1 Institute of Molecular Biology and Genetics of the NAS of Ukraine, Kyiv, Ukraine
2 Scientific Service Company «OTAVA», LLC, Kyiv, Ukraine
Abstract: Eleven spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives were synthesized, and their antifungal activity against Candida
albicans and Cryptococcus neoformans was tested. Among synthesized derivatives, one antifungal-active substance was revealed,
6-fluorospiro[chromane-2,3ʹ-pyrrolidine]-4-one hydrochloride inhibiting growth of Cryptococcus neoformans with the MIC value 16
μg/ml. This compound demonstrates no cytotoxicity or hemolytic activity against human cell line HEK-293 and red blood cells.
Keywords: spiro[chromane-2,3ʹ-pyrrolidine]-4-ones; synthesis; antifungal activity; Cryptococcus neoformans.
Introduction
Antimicrobial resistance (AMR) has been recognized by
the World Health Organization (WHO) as the one of the top
global public health and development threats [1] that world
encountered at the current stage of evolution of
microorganisms being forced to survive under widespread
overuse of antibiotics. AMR not just raises concern of
spreading infectious diseases itself, but moreover, renders
many of gains of modern medicine obsolete making many
medical procedures and treatments such as surgery,
caesarean sections and cancer chemotherapy much riskier.
One of the way of addressing AMR is through research
and development of new antimicrobials. Aiming at focus
these efforts on the crucial pathogens, WHO developed and
published the “WHO fungal priority pathogen list” [2].
Cryptococcus neoformans and Candida albicans selected
for our investigation are the pathogens from the most
threatening Critical Priority Group of this list.
Received:
Revised:
Accepted:
Published online:
29.04.2025
23.05.2025
28.05.2025
30.06.2025
Corresponding author. Tel.: +380-66-237-2022;
e-mail: vsapelkin@gmail.com (V.M. Sapelkin)
ORCID: 0000-0003-2248-1178
The spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives
demonstrate various biological activity. They were
developed as inhibitors of stearoyl-CoA-desaturase [3],
acetyl-CoA-carboxylase (ACC) [4], histone deacetylase [5]
and other targets, but never as antibiotics. At the same time
their close relative homologs, spiro[chromane-2,4′-
piperidine]-4-one derivatives recently were investigated as
potential inhibitors of fatty acid synthesis in pathogenic
microorganisms [6].
Here we are representing the synthesis of 11 novel
spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives and
evaluation of their antifungal activity.
Results and Discussion
All spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives
were synthesized starting from the corresponding 2-hydro-
xyacetophenones. 2-Hydroxy-5-methoxyacetophenone (1),
5-benzyloxy-2-hydroxyacetophenone (2) and 5-buthoxy-2-
hydroxyacetophenone (3) were synthesized by the alkylati-
on of 2,5-dihydroxyacetophenone with correspondingly
methyl iodide, benzyl chloride, and butyl iodide (Scheme 1)
according to the approach [7]. 2-Benzyoloxy-6-hydro-
xyacetophenone (4) was obtained in the same way by
reaction between 2,6-dihydroxyacetophenone and benzyl
chloride [8].
2-Hydroxy-5-fluoroacetophenone (5) was synthesized by
acetylation 4-fluorophenol and following Fries rearrange-
© Sapelkin V.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.
https://orcid.org/0000-0003-2248-1178
S.S. Tarnavskiy et al.
51
O
OH
HO
O
OH
R
1-4
R = 5-MeO (1); 5-BzlO (2); 5-BuO (3); 6-BzlO (4)
Scheme 1. Synthesis of 2-hydroxyacetophenones 1-4. Conditions a) K2CO3, acetone, 6h, reflux.
OH
R
O
R
O
OH
R
O
5-6
R = 5-F (5); 3-Et, 5-Br (6)
a b
Scheme 2. Synthesis of 2-hydroxyacetophenones 5-6. Conditions a) CH3COCl, 2h, r.t.; b) AlCl3, 130 °C, 2h.
O
OH
R N
OO
O
O
N
O
O
R
O
N+
O
R
-Cl
+
O
7-14
R = 6-MeO (7); 6-Br, 8-Et (8); H, 6-BuO (10); 7-OH (11); 6-OH (12);
5-BzlO (13); 6-BzlO(14); 6-F (15); 6-MeO (16); H (17).
a b
1-6 15-17
Scheme 3. Synthesis of spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives. Conditions a) MeOH, 200% mol. pyrrolidine, 4h, reflux;
b) HCl/dioxane, 1h, r.t.
ment [9]. 2-Hydroxy-3-ethyl-5-bromoacetophenone (6) was
obtained starting from 2-ethylphenol. The bromination
process was carried out according to the method [10], which
yielded 2-ethyl-5-bromophenol. Following acetylation, as
described in [9], 2-ethyl-5-bromophenyl acetate was
obtained. The Fries rearrangement in accordance with [9]
leads finally to 2-hydroxy-3-ethyl-5-bromoacetophenone
(6) (Scheme 2).
The corresponding Boc-protected spiro[chromane-2,3ʹ-
pyrrolidine]-4-one derivatives 7-14 were synthesized by the
condensation Boc-pyrrolidine-3-one with 2-hydroxy-
acetophenones in methanol solution catalyzed by
pyrrolidine [5]. The Boc-protection removal was carried out
using hydrogen chloride in dioxane giving amine
hydrochlorides 15-17 according to the Scheme 3.
Antifungal activity of 11 novel spiro[chromane-2,3ʹ-
pyrrolidine]-4-one derivatives 7-17 was tested at the
University of Queensland (Australia) in a framework of
CO-ADD (The Community for Antimicrobial Drug
Discovery), funded by the Wellcome Trust (UK) on
pathogenic strains Cryptococcus neoformans var. Grubii
ATCC 208821 and Candida albicans ATCC90028 [11].
Cytotoxicity and hemolysis assay of the synthesized
compounds were determined using human embryonic
kidney cells HEK-293 ATCC CRL-1573 and human red
blood cells.
Ten of investigated compounds demonstrate no
significant antifungal activity at the studied concentrations.
At the same time 6-fluorospiro[chromane-2,3ʹ-pyrrolidine]-
4-one hydrochloride (15) showed promising antifungal
activity against the Cryptococcus neoformans with MIC
value reaching 16 μg/ml. This compound doesn’t show
toxicity against human cells used in testing.
Conclusions
Eleven novel spiro[chromane-2,3ʹ-pyrrolidine]-4-one
derivatives have been synthesized. One of them, namely
6-fluorospiro[chromene-2,3ʹ-pyrrolidine]-4-one hydrochlo-
ride, exhibits antifungal activity against Cryptococcus
neoformans with a minimum inhibitory concentration
(MIC) value of 16 μg/ml and no cytotoxic or hemolytic
activity against human cells, making it a promising
compound for further studies in the field of structural
optimization and identification of its molecular target in
pathogenic fungi.
Experimental section
2-Hydroxyacetophenone, 2,4-dihydroxyacetophenone,
2,5-dihydroxyacetophenone, 2,6-dihydroxyacetophenone,
4-fluorophenol and 2-ethylphenol as well as Boc-
pyrrolidine-3-one were purchased from Acros Organics
BVBA. The structures of synthesized compounds have been
confirmed by 1H NMR spectra recorded on a Varian
MercuryVRX-400 instrument with an operating frequency
400 MHz and an internal standard TMS (tetramethylsilane).
High-performance liquid chromatography-mass
spectrometric analysis (LC-MS) was performed on Agilent
1100LC/MSD SL instrument (Agilent Technologies, USA)
equipped with Zorbax SB-C18 Rapid Resolution HT
Cartridge (2.1×30 mm, 1.8 µm) using a 0-100% gradient (2
min) of CH3CN in 0.1% formic acid.
ISSN 1814-9758. Ukr. Bioorg. Acta, 2025, Vol. 20, N 1
52
Synthesis
1-(5-Butoxy-2-hydroxyphenyl)ethanone (3) as well as
other 2-hydroxy-5- or 6-alkoxoacetophenones 1-4 were
synthesized by the alkylation of dihydroxyacetophenones
with corresponding alkyl halide following the procedure
described if reference [7]. Yield: 62%. Light brown powder.
M.p. 33-35 ºC. 1H NMR (400 MHz, DMSO-d6) δ 11.50 (s,
1H), 7.30 (d, J = 2.9Hz, 1H), 7.14 (dd, J = 8.8, 2.9 Hz, 1H),
6.88 (d, J = 8.8Hz, 1H), 3.93 (t, J = 6.6Hz, 2H), 2.63 (s,
3H), 1.67 (m, 2H), 1.43 (m, 2H), 0.93 (t, J = 7.3Hz, 3H).
LC-MS m/z (M+H)+ 209.
1-(5-Bromo-3-ethyl-2-hydroxyphenyl)ethanone (6) was
synthesized as it’s reported in [11]. Yield: 39%. Light
yellow liquid. 1H NMR (400 MHz, CDCl3) δ 12.438 (s,
1H), 7.648 (s, 1H), 7.403 (s, 1H), 2.637 (m, 5H), 1.221 (t, J
= 7.3Hz, 3H). LC-MS m/z (M+H)+ 244.
General procedure for synthesis of spiro[chromane-2,3ʹ-
pyrrolidine]-4-one derivatives.
10 mmol of corresponding 2-hydroxyacetophenone, 1.85
g (10 mmol) of N-Boc pyrrolidine-3-one and 1.67 mL (20
mmol) pyrrolidine dissolved in 10 ml of MeOH were heated
under reflux for 4 h. Then volatile material was evaporated
off under vacuum and the crude products we purified by
column chromatography (eluent: petroleum ether/EtOAc
95:5 to 7:3) to obtain 4-oxo-spiro(chromane-2,3′-
pyrrolidine)-1′-carboxylic acid tert-butyl esters 7-14.
tert-Butyl 6-methoxy-4-oxo-spiro[chromane-2,3'-pyrroli-
dine]-1'-carboxylate (7).
Yield: 57%. Brown powder. M.p. 115-117 ºC. 1H NMR
(400 MHz, DMSO-d6) δ 7.18 (d, J = 3.2Hz, 1H), 7.13 (dd, J
= 8.8, 3.2 Hz, 1H), 6.92 (d, J = 3.2Hz, 1H), 3.77 (s, 3H),
3.60 (m, 1H), 3.494 (m, 1H), 3.40 (m, 1H), 2.96 (m, 2H),
2.20 (m, 1H), 1.964 (m, 1H), 1.41 (d, 9H). LC-MS m/z
(M+H)+ 334.
tert-Butyl 6-bromo-8-ethyl-4-oxo-spiro[chromane-2,3'-
pyrrolidine]-1'-carboxylate (8).
Yield: 69%. White powder M.p. 93-95 ºC. 1H NMR (400
MHz, CDCl3) δ 7.83 (s, 1H), 7.43 (s, 1H), 3.83 (d, J = 11.7,
1H), 3.60 (m, 3H), 3.32 (m, 1H), 2.60 (m, 3H), 2.30 (m,
1H), 1.94 (m, 1H), 1.45 (s, 9H), 1.18 (t, J = 7.3 Hz, 3H).
LC-MS m/z (M-C4H9)+ 353.8.
tert-Butyl 4-oxospiro[chromane-2,3'-pyrrolidine]-1'-car-
boxylate (9).
Yield: 51%. Light brown powder. M.p. 106-108 ºC.
1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.3 Hz, 1H),
7.47 (m, 1H), 7.02 (m, 1H), 6.95 (d, J = 8.5 Hz, 1H), 3.75
(d, J = 12.9, 1H), 3.55 (m, 2H), 3.36 (t, J = 12.7 Hz, 1H),
2.92 (m, 1H), 2.78 (m, 1H), 2.30 (m, 1H), 1.90 (m, 1H),
1.46 (s, 9H). LC-MS m/z (M-C4H8)+ 248.
tert-Butyl 6-butoxy-4-oxo-spiro[chromane-2,3'-pyrroli-
dine]-1'-carboxylate (10).
Yield: 54%. White powder M.p. 74-76 ºC. 1H NMR (400
MHz, CDCl3) δ 7.23 (s, 1H), 7.04 (d, J = 8.2 Hz, 1H), 6.87
(d, J = 8.3 Hz, 1H), 3.94 (t, J = 6.3 Hz, 2H), 3.73 (dd, J =
12.7, 4.3 Hz, 1H), 3.53 (m, 2H), 3.43 (t, J = 12.9 Hz, 1H),
2.88 (dd, J = 17.1, 5.4 Hz, 1H), 2.75 (m, 1H), 2.29 (m, 1H),
1.88 (m, 1H), 1.75 (m, 2H), 1.47 (m, 11H), 0.99 (t, J = 7.3
Hz, 3H). LC-MS m/z (M-C4H8)+ 320.
tert-Butyl 7-hydroxy-4-oxo-spiro[chromane-2,3'-pyrroli-
dine]-1'-carboxylate (11).
Yield: 48%. White powder. M.p. 154-156 ºC. 1H NMR
(400 MHz, DMSO-d6) δ 10.34 (s, 1H), 7.58 (d, J = 8.3 Hz,
1H), 6.44 (d, J = 8.3 Hz, 1H), 6.25 (s, 1H), 3.52 (m, 2H),
3.34 (m, 2H), 2.79 (m, 2H), 2.19 (m, 1H), 1.94 (m, 1H),
1.42 (s, 9H). LC-MS m/z (M-C4H8)+ 264.
tert-Butyl 6-hydroxy-4-oxo-spiro[chromane-2,3'-pyrroli-
dine]-1'-carboxylate (12).
Yield: 50%. White powder M.p. 181-183 ºC. 1H NMR
(400 MHz, DMSO-d6) δ 9.12 (s, 1H), 7.07 (s, 1H), 6.94 (m,
1H), 6.78 (m, 1H), 3.59 (m, 1H), 3.43 (m, 2H), 3.27 (m,
1H), 2.90 (m, 1H), 2.78 (m, 1H), 2.19 (m, 1H), 1.92 (m,
1H), 1.41 (s, 9H). LC-MS m/z (M+H)+ 320.
tert-Butyl 5-benzyloxy-4-oxo-spiro[chromane-2,3'-pyrro-
lidine]-1'-carboxylate (13).
Yield: 54%. White powder M.p. 123-125 ºC. 1H NMR
(400 MHz, CDCl3) δ 7.53 (m, 2H), 7.32 (m, 4H), 6.54 (m,
2H), 5.17 (s 2H), 3.74 (m, 1H), 3.53 (m, 2H), 3.36 (t, J 12.5
Hz, 1H), 2.83 (m, 2H), 2.30 (m, 1H), 1.91 (m, 1H), 1.46 (s,
9H). LC-MS m/z (M+H)+ 409.8.
tert-Butyl 6-benzyloxy-4-oxo-spiro[chromane-2,3'-pyrro-
lidine]-1'-carboxylate (14).
Yield: 56%. White powder M.p. 90-92 ºC. 1H NMR (400
MHz, CDCl3) δ 7.36 (m, 6H), 7.14 (m, 1H), 6.91 (d, J = 8.5
Hz, 1H), 5.03 (s, 2H), 3.75 (m, 1H), 3.54 (m, 2H), 3.34 (t, J
= 11.5 Hz, 1H), 2.84 (m, 2H), 2.31 (m, 1H), 1.90 (m, 1H),
1.50 (s, 9H). LC-MS m/z (M-C4H8)+ 353.8.
General procedure for Boc-deprotection.
3 ml of 4M dioxane solution of hydrogen chloride was
added to solution of 3 mmol Boc-derivative in 9 ml of dry
dioxane. The mixture was stirred at the room temperature
until the starting material disappeared according to the TLC
data. The solution was evaporated, triturated with MTBE,
filtered off, washed with MTBE, and vacuum-dried. The
yield of hydrochlorides was almost quantitative.
6-Fluorospiro[chromane-2,3'-pyrrolidine]-4-one hydro-
chloride (15).
Yield: 95%. Brown powder. M.p. 192-194 ºC. 1H NMR
(400 MHz, DMSO-d6) δ 9.77 (s, 2H), 7.51 (m, 2H), 7.10
(dd, J = 8.7, 4.3 Hz, 1H), 3.52 (m, 1H), 3.27 (m, 1H), 3.18
(d, J = 17.1, 1H), 3.10 (d, J = 17.1, 1H), 2.30 (d, J = 17.1,
1H), 2.07 (m, 1H). LC-MS m/z (M+H-HCl)+ 222.
6-Methoxyspiro[chromane-2,3'-pyrrolidine]-4-one hyd-
rochloride (16).
Yield: 96%. Brown powder. M.p. 197-199 ºC. 1H NMR
(400 MHz, DMSO-d6) δ 9.65 (s, 2H), 7.24 (dd, J = 8.8, 3.2
Hz, 1H), 7.20 (d, J = 3.2 Hz, 1H), 6.99 (d, J = 8.8 Hz, 1H),
S.S. Tarnavskiy et al.
53
3.76 (s, 3H), 3.50 (d, J = 12.7 Hz, 1H), 3.39 (m, 1H), 3.25
(d, J = 12.7 Hz, 1H), 3.13 (d, J = 17.1, 1H), 3.04 (d, J =
17.1, 1H), 2.29 (m, 1H), 2.04 (m, 1H). LC-MS m/z (M+H-
HCl)+ 234.
Spiro[chromane-2,3'-pyrrolidine]-4-one hydrochloride
(17).
Yield: 92%. Light brown powder. M.p. 189-191 ºC.
1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 2H), 7.77 (dd, J =
7.8, 1.4 Hz, 1H), 7.62 (dt, J = 7,3 1.4 Hz, 1H), 7.11 (t, J =
7.3 Hz, 1H), 7.04 (d, J = 8.2 Hz, 1H), 3.50 (d, J = 12.4 Hz,
1H), 3.34 (m, 3H), 3.17 (d, J = 17.1 Hz, 1H), 3.06 (d, J =
17.1 Hz, 1H), 2.28 (m, 1H), 2.04 (m, 1H). LC-MS m/z
(M+H-HCl)+ 204.
Activity studies
To determine the minimum antifungal inhibitory con-
centration (MIC), cytotoxicity (CC50) on mammalian cells,
and hemolytic activity (HC10) on human erythrocytes,
solutions of compounds were prepared by sequential two-
fold dilutions (1:2) from 32 up to 0.25 μg/ml (or from 20 to
0.156 μM) of compounds tested.
Antimicrobial assays
Determination of antifungal activity of the newly
synthesized compounds was carried out according to the
standard protocols of the Community for Open
Antimicrobial Drug Discovery laboratory at The University
of Queensland (Australia). The minimal inhibitory
concentrations (MIC) were found at which complete/partial
inhibition of growth and reproduction of fungi was
observed. Two reference test strains of yeast-like fungi
(Candida albicans ATCC 90028, Cryptococcus neoformans
ATCC 208821) were taken. The work was performed using
384-well non-binding polystyrene plates (Fisher Scientific).
Such antimicrobial agents as amphotericin B and
fluconazole served as references. Cytotoxicity and
Hemolysis assay was carried out using HEK293 (human
embryonic kidney cells, ATCC CRL-1573) for cytotoxicity
and human blood erythrocytes (obtained from the
Australian Red Cross Blood Service) for hemolysis assays
according to known standard procedures.
Notes
Acknowledgments and finances. This work was
supported by the grants from the National Academy of
Sciences of Ukraine (0117U003914, 0122U201823). The
antifungal screening was carried out according to an
antimicrobial screening program [25] (The Community for
Open Antimicrobial Drug Discovery, CO-ADD) by the
Wellcome Trust (UK) and the University of Queensland
(Australia). The authors declare no conflict of interest.
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Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-
2,3ʹ-пірролідин]-4-ону
Сапелкін В.М.1*, Лукашов С.С.1, Бєда О.А.2, Ярмолюк С.М.1
1 Інститут молекулярної біології і генетики НАН України, Київ, Україна
2 ТОВ «Науково-сервісна фірма «ОТАВА», Київ, Україна
Резюме: Синтезовано одинадцять похідних спіро[хроман-2,3ʹ-пірролідин]-4-ону та вивчено їх протигрибкову активність щодо Candida albicans
та Cryptococcus neoformans. Знайдено, що сполука 6-флуороспіро[хромен-2,3ʹ-пірролідин]-4-он гідрохлорид активна проти Cryptococcus
neoformans та характеризується MIC 16 мг/мл. Водночас, ця речовина не виявляє цитотоксичної чи гемолітичної активності стосовно клітинної
лінії HEK-293 та еритроцитів людини.
Ключові слова: спіро[хроман-2,3ʹ-пірролідин]-4-они; синтез; протигрибкова активність; Cryptococcus neoformans.
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https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=20200116&CC=WO&NR=2020012422A1&KC=A1
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| id | oai:ojs2.bioorganica.com.ua:article-94 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:01:36Z |
| publishDate | 2025 |
| 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/e1/f113dd9f5d880cf3a45310ba43237ee1.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-942026-07-19T14:56:55Z Synthesis of some spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives and investigation of their antifungal activity Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону Sapelkin, Vladislav M. Lukashov, Sergiy S. Bieda, Oleksandr A. Yarmoluk, Sergiy M. spiro[chromane-2,3’-pyrrolidine]-4-ones synthesis antifungal activity Cryptococcus neoformans спіро[хроман-2,3ʹ-пірролідин]-4(3H)-они синтез протигрибкова активність Cryptococcus neoformans Eleven spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives were synthesized, and their antifungal activity against Candida albicans and Cryptococcus neoformans was tested. Among synthesized derivatives, one antifungal-active substance was revealed – 6-fluorospiro[chromane-2,3ʹ-pyrrolidine]-4-one hydrochloride inhibiting growth of Cryptococcus neoformans with the MIC value 16 μg/ml. This compound demonstrates no cytotoxicity or hemolytic activity against human cell line HEK-293 and red blood cells. Синтезовано одинадцять похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону та вивчено їх протигрибкову активність щодо Candida albicans та Cryptococcus neoformans. Знайдено, що сполука 6-флуороспіро-[хромен-2,3ʹ-пірролідин]-4(3H)-он гідрохлорид активна проти Cryptococcus neoformans  та характеризується MIC 16 мг/мл. Водночас, ця речовина не виявляє цитотоксичної чи гемолітичної активності стосовно клітинної лінії HEK-293 та еритроцитів людини. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2025-06-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/94 10.15407/bioorganica2025.01.050 Ukrainica Bioorganica Acta; Vol. 20 No. 1 (2025): Ukrainica Bioorganica Acta; 50-53 Ukrainica Bioorganica Acta; Том 20 № 1 (2025): Ukrainica Bioorganica Acta; 50-53 1814-9766 1814-9758 10.15407/bioorganica2025.01 en https://bioorganica.com.ua/index.php/journal/article/view/94/95 Copyright (c) 2025 Vladislav M. Sapelkin, Sergiy S. Lukashov, Oleksandr A. Bieda, Sergiy M. Yarmoluk https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | спіро[хроман-2,3ʹ-пірролідин]-4(3H)-они синтез протигрибкова активність Cryptococcus neoformans Sapelkin, Vladislav M. Lukashov, Sergiy S. Bieda, Oleksandr A. Yarmoluk, Sergiy M. Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону |
| title | Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону |
| title_alt | Synthesis of some spiro[chromane-2,3ʹ-pyrrolidine]-4-one derivatives and investigation of their antifungal activity |
| title_full | Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону |
| title_fullStr | Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону |
| title_full_unstemmed | Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону |
| title_short | Синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3H)-ону |
| title_sort | синтез та дослідження протигрибкової активності низки похідних спіро[хроман-2,3ʹ-пірролідин]-4(3h)-ону |
| topic | спіро[хроман-2,3ʹ-пірролідин]-4(3H)-они синтез протигрибкова активність Cryptococcus neoformans |
| topic_facet | spiro[chromane-2,3’-pyrrolidine]-4-ones synthesis antifungal activity Cryptococcus neoformans спіро[хроман-2,3ʹ-пірролідин]-4(3H)-они синтез протигрибкова активність Cryptococcus neoformans |
| url | https://bioorganica.com.ua/index.php/journal/article/view/94 |
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